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This page documents breaking multiple sclerosis news and research stories as they occur during the month.

For news and research for the previous 12 months please use the links on the menu on the left.

The news stories are taken from external sources and as such, MS-UK does not verify, endorse or accept responsibility for their content.

Some of these pages have been written for medical professionals and this can be reflected in the complexity of language and content. If you have any issues relating to the topics here, please call the MS-UK Helpline on 0800 7830 518.


Drug succeeds in trial(17/04/15)

An experimental drug comprising of a high-dose formulation of the food additive biotin has successfully helped patients with primary and secondary progressive MS in a major clinical trial, its French maker claims.

Biotin, also known as vitamin H, is already an approved food additive but the pharmaceutical-grade dose used in biotech company MedDay's drug MD1003 is 300 mg a day, which is 10,000 times the recommended daily food intake.

MedDay said a Phase III study with MD1003 met its goal of improving disability scores in patients after nine months and one year of treatment, potentially paving the way for the medicine to reach the market next year.

If all goes to plan, MedDay's drug could reach the market ahead of rival products in development at other companies, including Biogen's BII033, which is currently in Phase II clinical testing.

Although biotin is not a newly invented chemical, MedDay has U.S. and European patents protecting the dose and its use for MS.

Source: Reuters © Thomson Reuters 2015 (17/04/15)

Generic version of MS drug gets FDA approval(17/04/15)

The Food and Drug Administration has approved the first-ever generic version of the multiple sclerosis drug, Copaxone, which was developed by Momenta Pharmaceuticals. However, it’s still unclear when the drug might become available to patients.

Momenta developed the drug, to be marketed under the name Glatopa, in partnership with New Jersey-based generics company, Sandoz.

The original drug of which Glatopa is a generic version, called Copaxone, is marketed by Israeli drug firm Teva Pharmaceuticals and generated more than $4bn in revenue last year.

Momenta’s attempts to get approval of Glatopa have been tied up in patent battles with Teva. A statement from Momanta says only that Sandoz “is currently evaluating launch timing.”

Source: Boston Business Journal © 2015 American City Business Journals. (17/04/15)

National Theatre Assisted Performances(17/04/15)

The National Theatre has released the latest season listings for Assisted Performances at the National Theatre, through to July 2015. Some productions are provided with Audio-described performances and touch tours for Blind and visually impaired people, Captioned performances for deaf or partially hearing visitors and Relaxed performances are aimed at anyone who would benefit from a more relaxed performance environment including people with an Autistic Spectrum Condition, sensory or communication disorders, or a learning disability.

More information about Accessibility at the National Theatre, and individual listings of performances can be found here: http://www.nationaltheatre.org.uk/your-visit/access 

Source: The National Theatre 917/04/15)

Study suggests wearables could help MS patients(15/04/15)

A three-week study by Biogen and the American patient network PatientsLikeMe claims to have found patients with multiple sclerosis can benefit from a wearable device that tracks their activity, reports the Boston Business Journal.

Biogen and the patient platform, which collects and shares patient experiences on its website, conducted the study to show the feasibility of using wearables.

“MS impairs the ability to walk for many people with MS, yet we only assess walking ability in the limited time a patient is in the doctor’s office,” said Dr. Richard Rudick, vice president of value-based medicine at Biogen.

“Consumer devices can measure number of steps, distance walked, and sleep quality on a continuous basis in a person’s home environment. These data could provide potentially important information to supplement office visit exams.”

The study found patients were receptive to wearing a device and sharing their data, and said the device helped prompt patients to be more active and helped them manage their MS.

Of the 248 PatientsLikeMe members who were provided with activity trackers, 213 activated the device and authorized PatientsLikeMe to access their data. Another 203 tracked data on the device.

Source: Boston Business Journal © 2015 American City Business Journals (15/04/15)

New drug could reverse MS damage(15/04/15)

A new experimental drug, anti-LINGO-1, has been found to repair myelin and so radically improving nerve signalling, reports The Daily Telegraph.

The scientists studied patients who had optic neuritis – damage of the optic nerve.

The results showed 53 per cent of people on the drug saw their nerve signalling restored to normal or nearly normal while on average most saw signalling between the retina and the brain improve by 41 per cent.

Although the subjects tested were not actually diagnosed with multiple sclerosis, scientists say the new results prove anti-LINGO-1 can repair myelin, and so could help people with MS.

"This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain, and advances the field of neuro-reparative therapies," said study lead author Dr Diego Cadavid, of Biogen.

All patients involved in the trial were given the new drug or a placebo once every four weeks for a total of six doses.

Because optic neuritis only usually affects one eye, doctors evaluated the recovery of the optic nerve by comparing it with the normal healthy eye.

The scientists are now following up patients to find out of the signalling improvement will restored their vision.

"More studies are needed to evaluate whether these changes lead to clinical improvement," said Cadavid.

The drug works by targeting ‘Lingo-1’ a protein which stops nerve cells from developing further once the nervous system is fully formed.

By blocking that protein, the drug effectively tells the body to carry on growing the nerves, which repairs any damage.

Biogen chief medical officer Alfred Sandrock said “We believe the results are encouraging, as this is the first clinical trial to provide evidence of biological repair in the central nervous system by facilitating remyelination following an acute inflammatory injury”.

Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (15/04/15)

Beta-interferons ‘not associated with delayed onset of SPMS’(13/04/15)

A Canadian study has found no link between the delayed onset of secondary progressive multiple sclerosis and treatment with beta-interferons.

In the study, Beta-interferon Exposure And Onset Of Secondary Progressive Multiple Sclerosis, published in the European Journal Of Neurology, the researchers set out to examine the association between beta-interferons and the onset of secondary progressive MS in patients with relapsing-remitting MS.

Beta-interferons are the most widely prescribed drugs for patients with MS, but whether or not treatment with beta-interferons can delay the onset of secondary progressive MS onset has always been unclear.

The scientists took 794 patients with relapsing-remitting MS and compared them with a healthy control group. The outcome was gauged from the start of treatment with beta-interferons to confirmation of the onset of secondary-progressive MS.

In the published results, the researchers reported: “The median follow-up for the beta-interferon-treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching secondary progressive MS were 9.2 per cent, 11.8 per cent and 32.9 per cent, respectively. After adjustment for confounders, beta-interferon exposure was not associated with the risk of reaching secondary progressive MS when either the contemporary or the historical untreated cohorts were considered.”

The study concluded that, amongst patients with relapsing-remitting MS, use of beta-interferons was not associated with a delayed onset of secondary progressive MS.

Source: Eur J Neurol. 2015 Apr 6. doi: 10.1111/ene.12698. & PMID: 25846809 (13/04/15)

PML death linked to Tecfidera(10/04/15)

The brain infection progressive multifocal leukoencephalopathy (PML) has killed a Dutch psoriasis patient who was taking a high dose of a drug with ingredients similar to Tecfidera. Tecfidera is used for multiple sclerosis, which the Dutch patient didn’t have, and the medicine was made in a compounding pharmacy and not by Biogen. Yet, according to Bloomberg.com, doctors claim the case suggests the infection could emerge in people who aren’t showing warning signs.

The PML infection was detailed in the New England Journal of Medicine, accompanied by a separate report on a multiple sclerosis patient who died of PML while taking Biogen’s drug.

While physicians can monitor patients for signs of PML, the 64-year-old psoriasis patient didn’t have seriously low levels of infection-fighting white blood cells, thought to be an indicator of risk for PML.

The Dutch case is the first found in a person on dimethyl fumarate, the active ingredient in Tecfidera, who didn’t have early warning signs. That’s “a situation previously thought to be unlikely,” wrote Dennis Nieuwkamp and other doctors from the University Medical Center Utrecht, in the Netherlands.

It’s not appropriate to extrapolate the risks of a pharmacy-mixed drug to Tecfidera, said Catherine Falcetti, a Biogen spokeswoman. The pharmacy-made drug containing dimethyl fumarate, called Psorinovo, is an unregulated product and differs from Tecfidera based on the amount and nature of the active substances, as well as the specific formulation and doses, she said.

There has been only one case of PML in a Tecfidera patient, out of more than 135,000 who have received it. Doctors are told to monitor patients’ blood to detect low white cell counts, a known risk for PML, Falcetti said.

Since the number of people getting dimethyl fumarate is rapidly increasing because of Tecfidera, “our case raises important questions with respect to safety monitoring,” the Dutch doctors wrote.

The report isn’t likely to change use of Tecfidera, however, said Karen Blitz, director of the North Shore-LIJ Multiple Sclerosis Center in East Meadow, New York. The drug helps patients remain functional and many are willing to take risks for that benefit, she said. The danger is exceptionally rare, she added. “If there is another case in a patient taking the currently recommended dose of Tecfidera, that would be interesting,” said Blitz. “Unless there is more data indicating a risk, I’m going to continue to use the drug and monitor white blood cell counts.”

Source: Bloomberg Business ©2015 Bloomberg L.P (10/04/15)

America’s National MS Society invests $28m in new research(08/04/15)

America’s National Multiple Sclerosis Society has committed $28m to support an expected 84 new MS research projects and training awards, it has been revealed.

This financial commitment is the latest in the Society's projected investment of over $52m in 2015 to support 380 new and ongoing studies around the world.

Among the research projects are a University of California, San Francisco-led consortium focusing on a comprehensive analysis of the gut microbiome to develop probiotic strategies for stopping progressive MS; a pilot trial at Johns Hopkins University exploring the tolerability of a diet that intermittently restricts calorie intake as a treatment for disease activity in people with MS; pre-clinical studies by a commercial firm (Bionure) to test the potential of a compound to protect the nervous system and stimulate repair of nerve-insulating myelin; and a new collaborative center at Oregon Health & Science University to research patient-centered wellness programs to improve the daily life of people with MS.

"MS research is a top National MS Society priority, with increasing annual investments to drive solutions for every person with MS," said Cynthia Zagieboylo, President and CEO of the Society.

"We fund the entire research spectrum, propelling novel ideas into the lab, translating breakthroughs into clinical trials, and moving success in clinical trials into new treatments for people living with MS."

Source: PR Newswire Copyright © 2015 PR Newswire Association LLC (08/04/15)

Progressive MS treatment phase III study update(07/04/15)

MedDay, a biotechnology company focused on the treatment of nervous system disorders, has provided further information about the design of its pivotal clinical trial (MS-SPI) to investigate the efficacy and safety of MD1003 in the treatment of primary and secondary progressive multiple sclerosis.

MS-SPI is a randomised, double-blind, multicenter, placebo-controlled (2:1) trial of MD1003, 300 mg/day, in patients with progressive MS who have demonstrated progression in the two years prior to enrolment.

A total of 154 patients with a baseline EDSS (Expanded Disability Status Scale) score of between 4.5 and 7 were enrolled from 16 MS reference centres across France. Treatment duration was one year.

The primary endpoint for the study was defined as the proportion of patients who improved at nine months (M9), with confirmation at 12 months (M12). Improvement was defined as either a decrease in EDSS or an improvement in TW25 (a timed 25-foot walk) of at least 20 per cent. The comparison for each outcome was the best EDSS and TW25 scores obtained at the screening and randomisation visits.

The main secondary endpoints evaluate the effect of MD1003 in stabilising or slowing down the rate of progression. These endpoints include the change in EDSS between M0 and M12, the proportion of patients with progression at M9 confirmed at M12 and the change in TW25.

Frédéric Sedel, MD, Chief Executive Officer of MedDay, said: “This trial was particularly ambitious. This is the first time a study in progressive MS has evaluated the proportion of patients improved at M9 and confirmed at M12.”

MD1003 is an investigational medicine thought to have both pro-myelinotic effects and to enhance the supply of energy for nerve impulse transmission. MD1003 is an active pharmaceutical ingredient administered at a dose of 300 mg /day.

Source: Business Wire © 2015 Business Wire (07/04/15)

Patients could benefit from brain boost(07/04/15)

Multiple sclerosis patients could one day benefit from treatments that boost their brain function, a study has suggested.

Increasing the activity of neurons could be beneficial in people with the condition, researchers say. It could stimulate the production of a substance that protects nerve fibres.

The finding could pave the way for new treatments, researchers say. MS affects the brain and spinal cord and can cause problems with balance, movement and vision.

Information in the brain is transmitted along nerve fibres known as axons. A material - called myelin - forms a layer around axons, which keeps them healthy and helps speed up the transfer of information.

Damage to myelin contributes to diseases of the brain such as multiple sclerosis.

Until now, it was not known how brain activity controls production of myelin by specialist cells, researchers say.

Researchers examined how changes in the activity of neurons affects how much myelin is produced in the brains of zebrafish. Decreased brain function reduced the amount of myelin made, while production was increased by around 40 per cent when the neuronal activity of fish was increased, the team says.

Before they can develop new therapies, the team says it needs to learn more about how brain function controls the complex processes by which axons are coated with myelin.

The study, published in the journal Nature Neuroscience, was funded by The Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Lister Research Prize.

Dr David Lyons, of the University of Edinburgh's Centre for Neuroregeneration, who led the study, said: "We have a long way to go before we fully understand how our brain activity regulates myelin production, but the fact that this is even something that the brain can do is a good news story. We are hopeful that one day in the future we may be able to translate this type of discovery to help treat disease and to maintain a healthy nervous system through life."

Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (07/04/15)

Immune system component found to be related to MS neurodegeneration(07/04/15)

A study published in PLOS ONE provides new insights into the relationship between the immune system and neurodegeneration and clinical disability in MS, reports Multiple Sclerosis News Today.

A team of researchers led by Dr. Shahin Aeinehband from the Neuroimmunology Unit at the Karolinska Institutet in Sweden looked at the association between a central component of the innate immune system, C3 protein, with the activity of cholinergic metabolism and neurodegeneration markers in both relapsing-remitting and primary progressive MS.

In the study Complement Component C3 And Butyrylcholinesterase Activity Are Associated With Neurodegeneration And Clinical Disability In Multiple Sclerosis, Dr. Shahin Aeinehband and his team analysed 48 samples of cerebrospinal fluid (CSF) from MS patients and compared them to 18 samples of CSF from healthy individuals. Levels of C3 protein; neurofilament-light (NFL), a marker for ongoing nerve injury; and activity of the two main acetylcholine degrading enzymes, acetylcholinesterase and butyrylcholinesterase (BuChE) were measured.

C3 protein levels were elevated in MS patients when compared to controls and were correlated both to disability and neurodegeneration (as showed by NFL levels). This finding supports the theory that the complement system influences MS and is compatible with previous findings in other neurodegenerative conditions. Additionally, the C3 protein levels were increased in patients with more cerebral lesions on magnetic resonance imaging and in patients with progressive disease. Finally, BuChE activity correlated with both C3 and NFL levels in individual samples.

In conclusion, the study found that C3 protein is a marker for ongoing nerve injury and degree of disease disability, with this relationship appearing to be especially important in late stage disease (i.e., with more cerebral lesions or clinically progressive disease). It also suggests a link between the expression of complement C3 and the cholinergic tone (BuChE activity).

Although further studies are needed to clearly establish the cause of these processes, these findings can offer future novel targets for MS therapy.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (07/04/15)

MS patients less susceptible to gout claims study(07/04/15)

A group of researchers have been investigating the theory that high levels of uric acid, whch may have protective effects on neurons and are present in gout patients, could mean gout resulting in a reduced risk of developing neurological disease, reports Multiple Sclerosis News Today.

“This study investigated the epidemiological evidence for a protective role of high serum concentration of uric acid, for which we used gout as a proxy, in the aetiology of multiple sclerosis, Parkinson’s disease, or motor neuron disease,” wrote Dr. Pakpoor, who works alongside Dr. Michael J. Goldacre at the Unit of Health-Care Epidemiology in the University of Oxford. The article, “,” was published in the journal BMC Neurology.

Dr. Julia Pakpoor’s study, Clinical Associations Between Gout And Multiple Sclerosis, Parkinson’s Disease And Motor Neuron Disease: Record-linkage Studies, analysed patient records for hospital admissions and deaths in England between 1999 and 2012. Of approximately nine million hospital admissions, 214,653 were related to gout, 82,220 related to multiple sclerosis, 217,179 related to Parkinson’s disease, and 25,185 related to motor neuron disease.

When researchers analysed the long-term data from the study, patients with gout were not found to be less likely to develop multiple sclerosis. Although the odds ratios revealed a modest correlation between gout and subsequent multiple sclerosis, that observation was negated when the researchers only analysed neurological disease diagnosed within five years of a gout diagnosis.

On the other hand, patients with multiple sclerosis were less likely to experience gout, the study found.

Strengths of the study included a large sample size and a national representation of the population. However, since the study was not conducted in a cohort of patients, the researchers are limited in knowing if hospitalisations were “first ever” diagnoses. Additionally, gout is only a representation of increased serum uric acid, meaning the association between uric acid and neurological disease may be underestimated.

To remediate this limitation, the authors suggest the possibility of conducting a follow-up study of multiple sclerosis patients to identify the presence of gout or serum levels of uric acid over time.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (07/04/15)

Statins therapy yields conflicting results(02/04/15)

Researchers at the IRCCS Centro Neurolesi “Bonino-Pulejo” and the University of Messina in Italy have performed a review on the immunomodulatory activity reported for statins in the treatment of multiple sclerosis (MS) and on clinical trial results, reports Multiple Sclerosis News Today.

The study, Role Of Statins In The Treatment Of Multiple Sclerosis, was published in the journal Pharmacological Research.

Statins have been shown to have immunomodulatory and anti-inflammatory properties, making them an attractive therapeutic option for immune-mediated disorders such as MS.

Previous studies conducted in vitro and in animal models showed evidence that statins also have potential neuroprotective properties, although the mechanism behind it is poorly understood. Based on these three properties— immunomodulatory, anti-inflammatory and neuroprotective — they have now been tested in clinical trials as a therapy for MS, either alone or in combination with interferon-beta. Unfortunately, the translation of the results obtained in animal models with statins yielded conflicting results in human clinical trials.

Researchers found some clinical trial studies indicated oral statins were only partially effective as a monotherapy in the treatment of relapsing-remitting MS. When tested in combination with interferon-beta, some studies found an increase in clinical disease activity, relapses and new lesions in the brain. Other studies, however, have reported the combination therapy of statin and interferon-beta had no effect on relapse rate, neither on the development of brain lesions in patients with relapsing-remitting MS. Yet, other studies found statins offer clinical benefits in comparison with interferon-beta treatment alone, namely in the number of relapses and lesions in MS patients.

The research team concluded that the therapeutic combination of statins plus interferon-beta is apparently well-tolerated and safe but could not find decisive proof that statins and interferon-beta improves relapsing remitting MS outcomes in comparison to treatment with interferon-beta only.

The research team suggests further large, prospective, randomized, double-blind, placebo-controlled trials should be conducted to assess and provide definitive proof of whether statins are effective, either as monotherapy or combined with interferon-beta, as a treatment for MS.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (02/04/15)

New Multiple Sclerosis resource on healthtalk.org(02/04/15)

A new section has been added to healthtalk.org today to support family members and friends of people living with multiple sclerosis (MS).

The resource is based on the experiences of 40 people who shared their stories on film in interviews with University of Oxford researchers. Visitors to the website can find out what happens when a loved one has multiple sclerosis by reading about the experiences of others and watching clips from the interviews.

The new ‘MS: friends & family experiences’ section of healthtalk.org is comprised of 25 web pages and 250 video and audio clips and covers every aspect of life with multiple sclerosis from the point of view of friends and family, including topics such as social lives, relationships and feelings, as well as practical issues such as work, money, looking after home and family and home adaptations.

The research for the MS project was carried out by Nic Hughes, at the time a researcher from The Health Experiences Research Group (HERG) at the University of Oxford’s Nuffield Department of Primary care. Nic travelled around the country with a video camera, interviewing people in their own homes. Nic was supported in his research by a panel of expert including health professionals, researchers, interviewees from the project and a representative from the MS Society.

The group uses the same method for each health issue covered on healthtalk.org. Sara Ryan, Research Director for HERG explains “We use rigorous research methods to capture the full ranges of experiences a patient might expect, not just the more sensational stories or hearsay you might find online”. healthtalk.org (formerly healthtalkonline) is run by an online charity that provides information and support around health issues by sharing patient stories. “healthtalk.org was founded on the belief that patients can offer invaluable advice and wisdom to others that are going through the same thing.” says Jo Kidd, Communications Manager for the charity “People often tell us how relieved they feel to hear other people talk about their experiences, it reminds them that they aren’t alone.”

The new resource is available at: http://www.healthtalk.org/ms-friends-family

Soure: United Kingdom Multiple Sclerosis Specialist Nurse Association (UKMSSNA) (02/04/15)

Phase 1 trial completed(01/04/15)

Vaccinex, Inc. has today announced the successful completion of a multicenter phase 1, randomized, double-blind, placebo-controlled, single ascending-dose safety and tolerability study in adult patients with multiple sclerosis.

According to reports, a total of 50 patients took part in the trial to determine the safety and tolerability of the drug currently known as VX15/2503, a monoclonal antibody discovered, characterised, and successfully tested by Vaccinex in preclinical models of multiple sclerosis and Huntington's disease.

VX15/2503 was found to be well tolerated at dose levels of up to 20 mg/kg with no reports of treatment-related serious adverse events.

No maximum tolerated dose (MTD) was determined and no dose-limiting toxicities (DLTs) were observed.

A phase 2 clinical trial of the VX15/2503 antibody in Huntington's Disease is planned to begin in the first half of 2015.

Source: BioSpace Copyright © 2015 BioSpace.com (01/04/15)

New purification method promises affordable antibody production for conditions such as MS(01/04/15)

The Austrian Centre of Industrial Biotechnology (Acib) claims to have developed a new purification method for pharmaceutical produced antibodies that promises to effectively decrease the high prices of these drugs in the market reports Multiple Sclerosis News Today.

For the pharmaceutical industry, decreasing processing costs is contingent on optimizing the purification process of antibody production. Currently, the process is performed through a process called “protein A” affinity chromatography (which purifies and concentrates antibodies out of a mixture into a buffering solution) and accounts for about 80 per cent of all the production costs.

The new purification method, developed by the Austrian Centre of Industrial Biotechnology (Acib) and the University of Natural Resources and Life Sciences Vienna (BOKU), consists of a tubular reactor where a Calcium-Phosphate flocculation is applied followed by precipitation of the purified proteins by cold ethanol. The reactor is built as a double-pipe heat exchanger that works in counter-current flow.

The newly developed method boasts a significantly higher performance when compared to the current “protein A” affinity chromatography in both purification speed and antibody yields. An additional advantage is that the current system apparatus is easily transferred to the new system.

The Austrian Centre of Industrial Biotechnology (acib) is an international network composed of several universities and pharmaceutical industries, including the Universities of Innsbruck and Graz, Graz University of Technology, the University of Natural Resources, Vienna and Joanneum Research and pharmaceuticals such as BASF, DSM, Sandoz, Boehringer Ingelheim, Jungbunzlauer, voestalpine, 3M or Clariant.

As an international Research Centre for Industrial Biotechnology, acib scientists are devoted to developing new methods that are more economic and eco-friendly, in order to substitute current technologies.

Prof. Alois Jungbauer, acib scientist, commented in a press release, “Our method shows great potential as a new platform technology for the pharmaceutical industry.”

For almost forty years, Monoclonal antibodies have formed the basis for several experimental multiple sclerosis therapies. Researchers have favored their use due to the fact that they function well as a targeted treatment for the disease. While antibodies are often used in more progressive cases of MS, due to the fact that they must be administered intravenously and can lead to infusion reactions, acib’s new process for creating therapeutic antibodies could at the very least help to further develop their application for a larger percentage of the patient population.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (01/04/15)

‘Changing Places’(01/04/15)

This was initially a campaign set up to support people with ‘profound and multiple learning disabilities’ (PMLD) to gain access to public toilet’s appropriate to meet their needs. There are many people who need facilities that are ‘more than your standard wheelchair accessible toilet’, not just people with PMLD but those with CP, MS and other support needs.

A ‘Changing Places’ toilets facilities will include an overhead hoist (or mobile hoist if that is not possible), an adult size changing bench, room for two carers and a centrally placed toilet (amongst other fab equipment!).

The campaign has been very successful and there are now over 700 ‘Changing Places’ loos across the UK (with more planned!).

Their website states that there are 8,500 people with MS who would benefit from this level of accessibility.

The Changing Places website has an interactive map listing all the loos’ available and also a ‘postcode locator’.

It’s a great resource to promote and share.

http://www.changing-places.org/ 

Source: Changing Places (01/04/15)

MS drug 'may already be out there'(01/04/15)

Depression and heart-disease drugs are to be tested in a trial to find treatments for multiple sclerosis from existing medicines, reports the BBC.

There are currently no treatments in the secondary progressive stage of the condition and doctors hope the necessary drugs are already out there, but have never been tested on MS.

More than 400 people will take part in the trial at University College London and the University of Edinburgh.

Walking, balance, speech, and vision can all become impaired in the later stages of the disease.

There are treatments in the early phases of MS to prevent the frequency or severity of relapses but there is nothing once the symptoms progresses.

The MS-Smart trial will test the safety and effectiveness of three drugs used in other conditions:

Amiloride - licensed to treat heart disease

Fluoxetine - used in depression

Riluzole - for Motor Neurone Disease

They were identified after a review of previously published research into drugs that appear to protect the nerves from damage.

Researchers believe these treatments could slow down the progress of MS and the trial will be the first time they have been tested on such a large number of patients.

Dr Jeremy Chataway, a consultant neurologist and lead researcher on the trial based at UCL, said there was "huge unmet need".

He told the BBC: "It may be the case that we have already invented the drugs we need to treat MS.

"In the same way that aspirin was developed as a painkiller and is now used to treat stroke patients, we may well have invented the drugs that we need, we just don't know that they work in different situations than what they were invented for.

"One of the advantages is they are very cheap, and we know a great deal about them as they have been tested on millions of people around the world in their original indication.

"So it's much more of a running start when we use drugs that we aim to repurpose."

Prof Siddharthan Chandran, a clinical neurologist at the University of Edinburgh, said: "This is a landmark study that seeks to not only test three potential treatments, but also showcase a new approach to clinical trials for progressive neurological conditions."

MS-Smart is a phase two trial, making sure the drugs are safe and demonstrate sufficient effectiveness before they are tested in a larger number of people.

If successful, it could lead to new ways of using the existing drugs to modify the way the disease develops.

Source: BBC News © British Broadcasting Corporation 2015 (01/04/15)

Clues to 'brain fog' in chronic fatigue patients found in spinal fluid(01/04/15)

People with chronic fatigue syndrome show a distinct pattern of immune system proteins in their spinal fluid, reports HealthDay - a finding that according to researchers could shed light on the "brain fog" that marks the condition.

The new study found that, compared with healthy people, those with chronic fatigue syndrome had lower levels of immune-system proteins called cytokines in the fluid that bathes the spinal cord and brain.

The exception was one particular cytokine, which was elevated in not only people with chronic fatigue, but also those with multiple sclerosis.

The finding could offer clues as to why people with chronic fatigue syndrome typically have problems with memory, concentration and thinking, said lead researcher Dr. Mady Hornig, a professor at Columbia University's Mailman School of Public Health in New York City.

The study also bolsters evidence that some type of immune dysfunction underlies the puzzling disorder, Hornig said.

Chronic fatigue syndrome is known medically as myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS. In the United States, it affects up to 2.5 million people, according to the Institute of Medicine.

In February, the IOM released a report affirming chronic fatigue syndrome is a legitimate medical condition that many health professionals still misunderstand or even dismiss as a figment of patients' imagination.

For the new study, reported March 31 in the journal Molecular Psychiatry, Hornig's team studied spinal-fluid samples from 32 people with chronic fatigue syndrome, 40 with multiple sclerosis, and 19 healthy people.

Overall, the researchers found reduced levels of most cytokines in chronic fatigue syndrome patients' spinal fluid, versus the two other groups. But one cytokine, eotaxin, was elevated in people with chronic fatigue syndrome and those with multiple sclerosis.

The significance of that finding is not clear yet, Hornig said. But she said eotaxin is involved in allergy-like immune responses.

There are some similarities between MS and chronic fatigue syndrome, Hornig added. MS patients suffer fatigue, and the disease is believed to be caused by an abnormal immune reaction -- in this case, against the body's own nerve tissue.

The precise cause of chronic fatigue syndrome is far from clear, but in general, it's thought to involve some type of immune system dysfunction, Hornig explained.

In a recent study, her team found that in people who've had chronic fatigue syndrome for a relatively short time - fewer than three years - cytokine levels in the blood were actually elevated. They dropped again, though, in people who'd had the disease for a longer time.

People in the current study had had chronic fatigue syndrome for about seven years. So the relatively low cytokine levels in their spinal fluid "parallel" what was seen in the earlier study, Hornig said.

"I think what we're seeing is an immune system exhaustion over time," Hornig speculated.

The theory is that the immune system may initially go into overdrive against an invader - like a virus - and then be unable to dial itself down, Hornig explained. That could account for the high cytokine levels in people who've had chronic fatigue syndrome for a short time.

Over time, though, the immune system may essentially wear itself down, leading to weak responses to mild infections that a healthy immune system would readily handle, Hornig suggested.

One hope, Hornig said, is that these findings could lead to objective tests that can diagnose chronic fatigue syndrome early.

Understanding the biology of the disease could also lead to treatments, Hornig said.

"We can't promise this will translate into treatments around the corner," she said. "But we hope to start giving doctors some tools."

Source: HealthDay Copyright ©2015 HealthDay (01/04/15)

£1.1m study to reduce cognitive problems in people with MS(26/03/15)

Experts in Nottingham are leading a major new study into how people with multiple sclerosis (MS) could overcome problems with attention and memory associated to their condition.

The Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis (CRAMMS) trial will evaluate the effectiveness of new strategies to improve and compensate for these difficulties and aims to improve the quality of life for the patient.

The trial is being led by Nadina Lincoln, Professor of Clinical Psychology in the Division of Rehabilitation and Ageing at The University of Nottingham and Dr Roshan das Nair, consultant clinical psychologist at Nottingham University Hospitals NHS Trust and honorary Associate Professor in the University's Division of Rehabilitation and Ageing.

Funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, the trial will begin recruiting participants later this month.

Professor Lincoln said: "The purpose of our research is to help people with multiple sclerosis boost their everyday memory so they can get on with their lives and do the things that people take for granted, for example remembering to pick their children up from school, turning the stove off, or knowing where they have put things.

"It will also provide them with strategies to enable them to concentrate on information without getting distracted."

Memory and attention problems are common complaints for those who have multiple sclerosis. More than 100,000 people in the UK have multiple sclerosis and of these, 50,000 will have problems with attention and memory at some stage in the progression of their condition.

Very few people with multiple sclerosis get treatment for cognitive problems in usual clinical practice, despite some evidence that cognitive rehabilitation may help reduce problems in attention and everyday forgetting. However, cognitive rehabilitation for people with multiple sclerosis has not been demonstrated to be effective or cost-effective in large-scale randomised controlled trials.

The study will be exploring the benefits of using internal memory aids, such as mnemonics -- using patterns, words and images to remember details -- and external aids, such as diaries, mobile phones and cameras. The researchers will also be looking for other imaginative ways to help improve memory and reduce forgetting.

The study is being conducted in collaboration with Swansea University, Nottingham University Hospitals NHS Trust, Sheffield Teaching Hospitals NHS Trust, The Walton Centre NHS Trust, and University Hospitals Birmingham NHS Trust.

They will recruit 400 volunteers, aged 16 to 69 years, from NHS hospitals, rehabilitation centres, multiple sclerosis charities, and web forums. About half the volunteers will then receive a 10-week group intervention at one of the study centres in Nottingham, Sheffield, Liverpool and Birmingham. The groups will focus on strategies to improve attention and to reduce memory problems in daily life. The remaining volunteers will continue to receive their existing level of care.

If this study confirms the benefits of cognitive rehabilitation it could lead to a change in clinical practice in the NHS and abroad. The researchers will also use questionnaires to determine the cost-effectiveness of this intervention, and to get feedback from those taking part in the trial to establish if intervention improved their quality of life.

Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (26/03/15)

Exercise may improve cognitive performance in people with MS(25/03/15)

Background
Cognitive impairment is a major debilitating feature of multiple sclerosis, and is estimated to occur in more than 50% of people living with MS at some point during the disease. These cognitive impairments can appear as difficulties with learning and memory, and deterioration of executive functions, such as planning or decision-making, focusing attention, multi-tasking, and problem-solving. People living with cognitive deficits can experience greatly diminished quality of life and loss of independence while facing the realization that treatment options are few-and-far-between. There are currently no drug therapies available that can specifically treat cognitive impairments in people living with MS, and cognitive rehabilitation studies have shown mixed success to date.

One approach that is emerging as a promising strategy for treating cognitive dysfunction in MS is exercise training. There is compelling experimental evidence showing that specific types of exercise training can improve cognition in both the general population and in people with certain neurological conditions like stroke, traumatic brain injury, and schizophrenia. For people living with MS, there have been three controlled clinical trials that have examined the effects of exercise on some aspects of cognition, although the results so far have been mixed. Part of the reason for these inconclusive findings is that the types and intensities of exercise have yet to be standardized, making comparisons across studies difficult.

A study published in the Journal of Clinical and Experimental Neuropsychology by Dr. Robert Motl and colleagues examined the short-term effects of several types of aerobic and non-aerobic exercise training on cognitive performance in people living with relapsing-remitting MS.

The Study
The study was performed on 24 individuals with relapsing-remitting MS. The participants underwent assessment of disability status using the Expanded Disability Status Scale (EDSS); eligible participants needed to be able to walk with or without minimal assistance (e.g. cane or crutch) in order to be able to participate in the exercise routines.

The researchers used the modified-flanker test to assess each subject’s reaction time and accuracy in identifying a randomly-presented object while blocking out either helpful or distracting information on either side of the object. In other words, the test allowed the researchers to measure the participants’ attention and executive functions (i.e. ability to suppress information that is either related or unrelated to the task).

The procedure consisted of five sessions (one per week); the first session established the baseline for exercise endurance fitness and trained the participants in the modified-flanker test, and was followed by four testing sessions. For each testing session, participants took the modified-flanker test, followed by one of three exercises (treadmill walking, stationary bicycle, or guided yoga) or quiet rest. After completion of the exercise and a cool-down period, participants took the modified-flanker test again to determine whether the exercise training affected performance on the test. For each session, participants performed a different exercise, so that by the end of the experiment each participant performed every exercise in a random order.

Results
The researchers measured the effects of each type of exercise on participants’ performance in the modified-flanker test, and compared that to their performance after quiet rest. They found that treadmill walking improved reaction time on the test with no improvement in accuracy compared to quiet rest; the reaction time was particularly improved in trials where the target object was surrounded by distracting information.

Both stationary bicycling and guided yoga also improved test reaction time without improving accuracy compared to quiet rest, although the reaction time improvements were not seen in trials where the target object was surrounded by distracting information.

Comment
The results of this study show that several types of exercise can improve cognitive performance and executive functions in people with relapsing-remitting MS. Treadmill walking in particular appeared to have the strongest effect on improving selective attention and blocking distracting information in this study; although the reason for this is unclear, the authors suggested that since impaired ambulation is so common in people with MS, treadmill walking perhaps stimulates those parts of the brain involved in attention to a greater degree than stationary cycling or yoga. The improvements in test performance were only seen in reaction time and not accuracy, although accuracy scores at baseline were already quite high, so there was very little room for improvement. A limitation of this study was that overall, the participants were not cognitively impaired, and it remains to be seen how people affected by MS with cognitive impairment could benefit from exercise training, as well as how to adapt exercise training in those with severe physical disability who cannot carry out these exercises.

The findings from this study contribute to a growing body of literature linking physical activity to neuroplasticity in the brain, both in the general population and in people living with MS. While the bulk of this research has looked at ways of harnessing neuroplasticity for promoting physical rehabilitation, an emerging area of study is the application of exercise interventions to improving cognitive impairment. Visit the research blog to learn more about neuroplasticity in MS.

Source
Sandroff BM et al. (2015) Acute effects of walking, cycling, and yoga exercise on cognition in persons with relapsing-remitting multiple sclerosis without impaired cognitive processing speed. J Clin Exp Neuropsychol. 37(2):209-19

Source: MS Society of Canada © 2015 MS Society of Canada (25/03/15)

Researchers welcome new funding to investigate link between virus and MS(24/03/15)

Murdoch University researchers have received funding to investigate the link between the Epstein-Barr virus infection, more commonly known as glandular fever or the ‘kissing disease’, and the debilitating disease Multiple Sclerosis (MS).

Dr David Nolan, Adjunct Associate Professor at the Institute of Immunology and Infectious Diseases (IIID) at Murdoch University, is the lead researcher and recipient of a $150,000 two-year project grant from MS Research Australia.

Dr Matthew Miles, Chief Executive Officer, MS Research Australia said more than 23,000 people in Australia have MS which is a chronic disease that attacks the central nervous system, affecting the brain, spinal cord and optic nerves.

“Through the research funding Dr Nolan will be able to investigate how a common virus interacts with the immune system of people with MS,” Dr Miles said.

“His research will provide greater understanding of the causes of MS, and will help to guide the development of potential new monitoring and treatment options.”

Dr Nolan said this research follows on from a previous project that was funded by the McCusker Foundation and looked at the risk factors, including viral infections, on the development of MS.

“It appears that there is a strong association between the Epstein-Barr virus and MS but it’s too early to say if it is the cause,” Dr Nolan said.

“We know that the Epstein-Barr virus specifically infects immune cells that produce antibodies, B cells, essentially hiding away within the immune system.

“For reasons that are still poorly understood, it seems that those affected by MS have an abnormal response to this virus and that the nervous system might be unintentionally targeted by the immune system as part of this response.

“If we can find a way to identify these infected B cells then we can study them in more detail, and also investigate the possibility of targeting our treatment approaches to these particular cells.

“The long-term goal is to halt the progression of MS by developing treatment strategies that interfere with the underlying disease mechanism.”

Over the next two years the research will focus on developing approaches that can identify the cells that are infected with Epstein-Barr virus.

“The research funding gives us a chance to make a real step forward in understanding the basis of Multiple Sclerosis and therefore improving both disease monitoring and treatment,” Dr Nolan said.

“We are thankful for the opportunity provided to us by MS Research Australia to continue with this exciting work.”

Source: News-Medical.net Copyright 2000-2015 AZoM.com Limited (24/03/15)

Possible biomarker for Tysabri response in MS(18/03/15)

Abstract

Hematopoietic mobilization: Potential biomarker of response to natalizumab in multiple sclerosis.

Mattoscio et al.

OBJECTIVE: To ascertain the mobilization from the bone marrow and the functional relevance of the increased number of circulating hematopoietic stem and progenitor cells (HSPC) induced by the anti-α-4 integrin antibody natalizumab in MSers.

METHODS: We evaluated CD45lowCD34+ HSPC frequency by flow cytometry in blood from 45 natalizumab-treated MSers (12 of whom were prospectively followed during the first year of treatment as part of a pilot cohort and 16 prospectively followed for validation), 10 untreated MSers with MS, and 24 healthy donors. In the natalizumab-treated group, we also assessed sorted HSPC cell cycle status, T- and B-lymphocyte subpopulation frequencies (n = 29), and HSPC differentiation potential (n = 10).

RESULTS: Natalizumab-induced circulating HSPC were predominantly quiescent, suggesting recent mobilization from the bone marrow, and were capable of differentiating ex vivo. Circulating HSPC numbers were significantly increased during natalizumab, but heterogeneously, allowing the stratification of mobilizer and non-mobilizer subgroups. Non-mobilizer status was associated with persistence of disease activity during treatment. The frequency of B cells and CD103+CD8+ regulatory T cells persistently increased, more significantly in mobilizer MSers, who also showed a specific naive/memory B-cell profile.

CONCLUSIONS: The data suggest that natalizumab-induced circulating HSPC increase is the result of true mobilization from the bone marrow and has clinical and immunologic relevance. HSPC mobilization, associated with clinical remission and increased proportion of circulating B and regulatory T cells, may contribute to the treatment's mode of action; thus, HSPC blood counts could represent an early biomarker of responsiveness to natalizumab.

Source: Neurology. 2015 Mar 11. © 2015 American Academy of Neurology.(18/03/15)

Promising prevention method found(17/03/15)

Scientists at the Walter and Eliza Hall Institute in Australia have developed a new drug-like molecule which can halt inflammation and has shown promise in preventing the progression of MS, reports Business Insider Australia.

Dr Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume Lessene, Professor Andrew Lew and colleagues say the molecule inhibits a key signal which triggers inflammation.

“Inflammation results when our immune cells release hormones called cytokines, which is a normal response to disease,” Dr Nachbur said. “However when too many cytokines are produced, inflammation can get out-of-control and damage our own body, all of which are hallmarks of immune or inflammatory diseases.”

To apply the brakes on this runaway immune response, institute researchers developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signalling protein called RIPK2. This prevents the release of inflammatory cytokines.

The molecule is seen as a great starting point for a drug discovery program which may one day lead to new treatments for MS and other inflammatory diseases.

The research is published in the journal Nature Communications.

Source: Business Insider Australia © 2007-2015 Allure Media (17/03/15)

Can emotional health influence MS treatment outcomes?(16/03/15)

Emotional health is important when battling any illness, writes Multiple Sclerosis News Today, but despite this sometimes the benefits of emotional health are overlooked by healthcare providers. Excessive stress can lead to anxiety and depression, which increases hormones such as adrenalin and glucocorticoids that shut down the immune system. Glucocorticoids have well-known negative effects on the nervous system.

Two research teams, including one supported by America’s National MS Society, are now studying ways to increase emotional wellness in people with MS.

Kimberly Beckwith McGuire, PhD, and her co-workers at the Kessler Institute for Rehabilitation in West Orange, NJ, have published a recent report on their evaluation of a psychoeducational MS wellness program in the International Journal of MS Care. The scientists studied forty-three people with MS who participated in a 10-week wellness program. The program involved 90-minute group sessions aimed at increasing awareness of social, intellectual, emotional, and spiritual factors. Eleven people with MS who were not in the program served as controls. The subjects filled out surveys to assess depression, anxiety, stress, cognition, pain, social support, and fatigue.

The group participating in the wellness program experienced statistically significant reductions in depression, anxiety, overall mental health, perceived stress, and pain compared to the controls. The program could serve as a model for the supplemental treatment of people with MS in general.

A second study published in BioMedCentral Psychiatry by Dr. Keryn L. Taylor and collaborators examined 2,459 people with MS who filled out an online survey capturing information on demographics, diagnostic history, level of disability, conditions occurring alongside MS, fatigue, depression and lifestyle and health behaviours.

About one-fifth of people in this study had depression. Within that group, about 93 per cent had clinically significant fatigue. Poor diet seemed to increase the risk for depression. In fact, dietary factors also decreased the risk for depression, including taking omega-3 fatty acids (particularly flaxseed oil) supplements and vitamin D supplements, eating fish regularly, meditating, and consuming moderate alcohol.

The results of these two studies are promising and underscore the importance of not just managing the symptoms of MS, but also paying attention to emotional health and lifestyle factors.

Further research on lifestyle factors and their impact on MS is a priority of the National MS society, so additional studies of this nature are likely in the works. Hopefully this research will have a positive impact on improving the quality of life of those with the disease.

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (16/03/15)

Depression modified by CBT in patients with MS(16/03/15)

An online program based on principals of cognitive behavioral therapy may be beneficial for depression in patients with multiple sclerosis who are unable to attend regular therapy sessions due to mobility issues, according to a new study Fischer A, et al. Lancet Psychiatry. 2015;doi:10.1016/S2215-0366(14)00049-2.

Deprexis (Gaia AG), the program used for the study, consisted of modules to address: psychoeducation, behavioral activation, cognitive modification, mindfulness and acceptance, interpersonal skills, relaxation, physical exercise and lifestyle modification, problem solving, expressive writing and forgiveness, positive psychology, and emotion-focus interventions.

Ninety patients aged 18 to 65 were randomly assigned to the intervention or waitlist control group for nine weeks. Of those, 35 in the intervention group and 36 in the control group finished the trial.

Patients’ Beck Depression Inventory scores appeared to decrease in the intervention group, and increase in the control group, with a mean group difference of − 4.02 points.

“Our findings show that a fully automated, internet-based cognitive behavioral therapy intervention is feasible and effective in patients with multiple sclerosis and self-reported depressive symptoms, adding to evidence that CBT is an effective treatment strategy in multiple-sclerosis-associated depression,” the researchers wrote.

Source: Healio Psychiatric Annals © 2015 Healio (16/03/15)

New inhibitor for treatment of inflammatory diseases (16/03/15)

Scientists have developed a new inhibitor for the treatment of inflammatory diseases. They have come up with a potent, selective, small-molecule inhibitor called MCC950. MCC950 is the inhibitor of NLRP3, a NOD-like receptor (NLR) family, pyrin domain–containing protein 3 inflammasome. NLRP3 inflammasome s a component of the inflammatory process, and its activation is pathogenic in conditions like multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis.

The results have been published in Nature Medicine and could prove to be a therapy for various conditions in the future. MCC950 specifically inhibits only NLRP3 and not other inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

Dr. Rebecca Coll, from UQ’s Institute for Molecular Bioscience, said “Inflammatory diseases result when our immune system is unable to switch off and so causes chronic inflammation in the body. Current therapies for inflammatory diseases, such as asprin, ibuprofen and steroids, don’t work well in severe cases and are not targeted, which can limit their effectiveness and cause side-effects. We now know that MCC950 can block an important component of the immune response — an inflammasome called NLRP3 that ‘switches on’ inflammation in our immune cells.”

Researchers hope this development would help in treating patients diagnosed with Cryopyrin-Associated Periodic Syndromes (CAPS), a family of rare and severe autoinflammatory diseases caused by a genetic mutation to NLRP3. Professor Luke O’Neill, Co-author and from Trinity College Dublin said, “We are excited about MCC950, which we believe has real potential to benefit patients suffering from several highly debilitating diseases, where there is a dire need for new medicines.”

Source: biotechin.asia (16/03/15)

Blood pressure drug protects against symptoms of MS in animal models(13/03/15)

An FDA-approved drug for high blood pressure, guanabenz, prevents myelin loss and alleviates clinical symptoms of multiple sclerosis (MS) in animal models, according to a new study at the University of Chicago in Nature Communications. The drug appears to enhance an innate cellular mechanism that protects myelin-producing cells against inflammatory stress.

"Guanabenz appears to enhance the cell's own protective machinery to diminish the loss of myelin, which is the major hallmark of MS," said senior study author Brian Popko, PhD, Jack Miller Professor of Neurological Disorders at the University of Chicago "While there have been many efforts to stimulate re-myelination, this now represents a unique protective approach. You don't have to repair the myelin if you don't lose it in the first place."

Multiple sclerosis is characterized by an abnormal immune response that leads to inflammation in the brain and the destruction of myelin - a fatty sheath that protects and insulates nerve fibers. MS is thought to affect more than 2.3 million people worldwide and has no known cure.

Popko and his colleagues have previously shown that oligodendrocytes, the brain cells which produce myelin, possess an innate mechanism that responds to stressors such as inflammation. It temporarily shuts down almost all normal protein production in the cell and selectively increases the production of protective proteins. When this mechanism is malfunctioning or overloaded - by the chronic inflammation seen in MS, for example - oligodendrocyte death and demyelination is significantly increased.

A recent study found evidence that guanabenz, a drug approved for oral administration for hypertension, enhances this stress response pathway independent of its anti-hypertension actions. To test the suitability of guanabenz as a potential treatment for MS, Popko and his team exposed cultured oligodendrocyte cells to interferon gamma - a molecule that increases inflammation - resulting in greatly increased myelin loss and cell death.

Treating these cells with guanabenz prevented myelin loss and restored cell survival to near normal levels. Oligodendrocytes that were not exposed to interferon gamma were unaffected by guanabenz, suggesting that it enhances only an active stress response pathway.

The team then tested the drug on multiple mouse models of MS. When treated with guanabenz, mice that are genetically engineered to express high amounts of interferon gamma in their brains were protected against oligodendrocyte and myelin loss. Treated mice retained several times more myelination and oligodendrocytes than untreated mice.

To study a chronic model of MS, the researchers immunized mice with a component of myelin, triggering an immune response against myelin similar to MS in humans. Clinical symptoms developed, but guanabenz administered a week after immunization significantly delayed the onset of these symptoms and reduced peak severity. Treatment also prevented around 20 percent of mice from developing symptoms at all.

To study the suitability of guanabenz as a therapeutic after MS symptoms have already appeared and peaked, the researchers used a mouse model in which symptoms relapse and remit - cycling from high severity to low severity to high again over time. They administered guanabenz immediately after symptoms peaked, and found a nearly 50 percent reduction in severity during the next relapse cycle.

"Human MS predominantly follows a relapsing-remitting pattern," said co-author Sharon Way, PhD, a National MS Society Postdoctoral Fellow at the University of Chicago. "Our hope is that this approach would provide protection against future relapses by making them milder and less frequent."

The team confirmed that guanabenz acts by temporarily blocking the reactivation of a protein known as eukaryotic translation initiation factor 2 (eIF2α). When deactivated, eIF2α initiates the stress response pathway. Blocking its reactivation results in a prolonged stress response and provides protection against cell death. The researchers hypothesize that guanabenz stimulates a protective cascade - because fewer oligodendrocytes die, less immune cells are recruited to the brain, which results in a decreased inflammatory response and preservation of myelin levels.

The Myelin Repair Foundation, which funded this work as part of a multi-institutional effort to accelerate research and development of treatments for MS, has entered into a cooperative agreement with the National Institutes of Health to assess guanabenz as a therapeutic candidate in MS clinical studies.

"Guanabenz will probably not be a standalone drug, but we hope that it can be developed for use in combination with other medications," Popko said. "Some current treatments can have severe side effects - for example dangerous infections in the brain. It would be of tremendous benefit for patients to have effective, less-risky therapies.

Source: MedicalXpress © Medical Xpress 2011-2014, Science X network (13/03/15)

MS fatigue ‘depends on task length’ (13/03/15)

Fatigue exhibited by multiple sclerosis (MS) patients is related to the task they are involved in, according to findings published in Frontiers in Neurology.

Researchers from the Kessler Foundation compared 32 MS patients and 24 healthy controls who completed experimental tasks in order to investigate the relationship between subjective and objective cognitive fatigue, information processing domain, cognitive load, and time on task in patients with MS. Participants completed tasks and were measured for processing speed (PS) and working memory (WM) using an analog scale at baseline and at multiple time points through the duration of the experiment. All of the patients in the study were right handed, and were at least 1 month from their last exacerbation (for only MS patients). Over a 2 week period, patients were evaluated over 2 separate sessions.

The participants completed WM tasks using building blocks and were instructed to respond when certain letters appeared. Fatigue levels were measured throughout the different tasks. At the same time, participants were asked about their feelings of fatigue at specific points of time when asked by the researchers, and they were instructed to ignore that fatigue up to that point of being asked.

The MS patient group demonstrated high fatigue than the control group across sample tasks. But, the researchers noted, there was no association between any of the other independent variables in the MS patient group.

“Task length was the factor associated with subjective cognitive fatigue which supports the hypothesis of Temporal Fatigue,” explained lead author Joshua Sandy, PhD, in a press release. “This finding should be considered when designing cognitive studies in MS populations. More research is needed to look at these parameters in people with different types of MS, different levels of cognitive impairment and in more advanced stages.”

The researchers wrote they believed that researchers should consider sustained task length when investigating cognitive fatigue and that further research is needed to confirm the hypothesis.

“The present findings suggest that MS participants experience subjective cognitive fatigue as the time of the task increased, regardless of the cognitive domain, and regardless of the cognitive load associated with the task,” the authors concluded. “Additionally, the MS group may have had to work harder than the HC group to achieve equivalent performance, and this extra effort resulted in higher fatigue. It remains possible that cognitive fatigue increased as a result of cognitive load or cognitive domain; however, this may have resulted in participants exerting more effort to maintain efficient performance.”

Source: MD Copyright HCPLive 2006-2015 Intellisphere, LLC (13/03/15)

Novel switch for autoimmune diseases could play role in MS(13/03/15)

Scientists at America's National Institutes of Health (NIH) say they may have discovered a critical immune system switch that could affect genes involved in autoimmune diseases. The ground-breaking work, published in the journal Nature, may be useful for developing treatments for autoimmune disorders such as multiple sclerosis (MS).

Finding autoimmune disease susceptibility genes, such as those involved in MS, is difficult due to environment-gene interactions that likely occur. Switches to control gene activities, known as enhancers, have been proposed to play a possible role.

Led by John J. O’Shea, M.D., the scientific director at NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, the researchers decided to study a newly discovered type of enhancer called a super-enhancer (SE). SEs are powerful switches that control genes. Dr. O’Shea and his collaborators looked for SEs in T cells, immune cells that are important for contributing to the autoimmune disease rheumatoid arthritis.

“We now know more about the genetics of autoimmune diseases,” stated NIAMS Director Stephen I. Katz, M.D., Ph.D. “Knowledge of the genetic risk factors helps us assess a person’s susceptibility to disease. With further research on the associated biological mechanisms, it could eventually enable physicians to tailor treatments to each individual.”

“Rather than starting off by looking at genes that we already knew were important in T cells, we took an unbiased approach,” remarked Dr. O’Shea. “From the locations of their super-enhancers, T cells are telling us where in the genome these cells invest their assets—their key proteins—and thereby where we are most likely to find genetic alterations that confer disease susceptibility.”

The researchers searched the genetic material of T cells and found that many identified mutations associated with autoimmune diseases could be localized to T cell SEs. The scientists then treated human T cells with a drug used for rheumatoid arthritis, called tofacitinib. They discovered that genes controlled by SEs changed dramatically compared to other genes without SEs. They concluded that tofacitinib may work by acting on SEs to affect T cell genes.

“Three types of data — the genetics of rheumatoid arthritis, a genomic feature of T cells, and the pharmacological effects of a rheumatoid arthritis drug—are all pointing to the importance of super-enhancers,” said lead author, Golnaz Vahedi, Ph.D. “These regions are where we plan to search for insights into the mechanisms that underlie rheumatoid arthritis and other autoimmune diseases, and for novel therapeutic targets for these conditions.”

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (13/03/15)

Compston wins Prize for MS Research(12/03/15)

The American Academy of Neurology (AAN) and America's National Multiple Sclerosis Society are to award the 2015 John Dystel Prize for MS Research to Alastair Compston, MBBS, PhD, Professor of Neurology at the University of Cambridge.

Compston will receive the award at the Academy's 67th Annual Meeting in Washington, DC, in April. The Annual Meeting is the world's largest gathering of neurologists with more than 12,000 attendees and more than 2,500 scientific presentations on the latest research advancements in brain disease.

The John Dystel Prize recognizes a significant contribution to research in the understanding, treatment or prevention of multiple sclerosis (MS).

Compston's research focuses on the evolution of ideas on the way multiple sclerosis develops. At this year's AAN Annual Meeting, Compston will discuss work in clinical science addressing hypotheses developed in the 1980s that pioneered the development of a highly effective mechanism-based therapy for patients with relapsing-remitting multiple sclerosis.

"The advances in treatment of multiple sclerosis seen in the last 20 years have been remarkable and unmatched by therapies developed for any other neurological disease," said Compston.

"I am conscious of the enormous contributions made by many clinicians, scientists and people with multiple sclerosis who enabled the successful outcome of this work."

Source: News-Medical.net AZoM.com Limited Copyright 2000-2015 (12/03/15)

Patient taking Gilenya contracts PML(10/03/15)

A woman in a Gilenya after-market study says the company didn’t notify all participants about a new case of progressive multifocal leukoencephalopathy (PML).

Novartis executives have confirmed a multiple sclerosis patient has developed the brain infection after taking their drug Gilenya for more than four years.

PML is a reactivation of the John Cunningham virus (JCV). JCV lives in the bodies of more than 75 percent of people in the United States. Most people’s immune systems are strong enough to keep the virus at bay.

The Switzerland-based pharmaceutical company posted a notice on their website announcing the development. The website notice said the patient is doing well. It said the patient had been taking Gilenya for an extended period when he or she contracted PML.

A company spokesman said Novartis officials were not available to comment on the case.

In late October, a patient in Europe died from PML after taking Tecfidera for more than four years. Biogen Idec Inc. manufactures that MS drug.

In 2013, the Food and Drug Administration (FDA) sent out an alert after a patient in Europe developed PML after taking Gilenya for eight months.

In their web posting, Novartis officials noted Gilenya has a “positive benefit-risk profile” in relapsing-remitting MS patients based on experience with 114,000 people who have taken the drug.

One woman who is part of a current Gilenya after-market extension study said she learned about the most recent PML case after Novartis contacted another person in the study. The woman then found the announcement on the company’s website.

The woman in the extension study, who has MS, said she was well aware of the remote possibility of contracting PML while taking Gilenya, so she wasn’t surprised by the announcement. She claimed Novartis did not contact everyone in her study group or update their informed consent documentation.

“I’m not upset, but I am disappointed,” the woman said.

People with weakened immune systems are at greater risk. That group includes people with AIDS, cancer patients taking chemotherapy drugs, transplant patients on anti-rejection drugs, and people taking immune-suppressing drugs for autoimmune conditions.

Source: Healthline Copyright © 2005 - 2015 Healthline Networks, Inc (10/03/15)

Could molecules prevent MS damage?(09/03/15)

Researchers at the Icahn School of Medicine at Mount Sinai have identified new compounds that could protect from multiple sclerosis-related damage, based on studies in mice with nervous system damage, mimicking MS. The study appeared in the journal Nature Neuroscience.

Jeffery Haines, PhD, a post-doctoral fellow at Mount Sinai and the study’s lead author commented, “The compounds identified in this study, when administered orally, both reduced the inflammation that is a hallmark of multiple sclerosis and protected against the nerve cell damage seen in mouse models of the disease. The multiple sclerosis drugs currently on the market and being tested elsewhere seek to reduce the immune attack on cells, but none target neurodegeneration nor do they work to restore nerve cell function. The findings of this new study represent an exciting step in the process of advancing new oral treatment options.”

A molecule called XPO1 (also called CRM1,) may be involved in multiple sclerosis as well as other diseases. The researchers decided to target this molecule.

They tested whether drugs designed to block XPO1/CRM1 could stop MS in mouse models. Two drugs were identified, KPT-276 and KPT-350, that acted on XPO1/CRM1. The medications seemed to protect cells from what is called free-radical damage — the production of damaging ions faster than the body can remove them. Free radical damage may be one way that the nervous system is affected in MS. Not only did the medications block free radical damage, they also prevented inflammation by stopping cells involved in inflammation from dividing. Immune cells can cause inflammation, which may be positive in infection, but is damaging in MS in which the immune cells attack the body’s own myelin. Stopping immune cells in the case of MS is therefore positive.

The medications helped the mice, which lost movement due to an experimental treatment that damaged myelin, to regain some movement as well.

Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomic Sciences at Mount Sinai and senior author of the study noted, “The study results elucidate the molecular mechanisms underlying disease progression in multiple sclerosis models, providing a basis for future clinical trials to determine safety and efficacy of these chemical agents in humans with demyelinating disorders.”

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (09/03/15)

Exercise bike pedals hope(09/03/15)

Researchers from the University of Sydney have designed an innovative exercise system that allows people with multiple sclerosis to workout their paralysed leg muscles in the hope of improving symptoms and slowing the disease progression.

The specially-designed exercise bike uses electrical stimulation to activate contractions in the major leg muscles, which forces the pedals to rotate.

Lead researcher Dr Ché Fornusek, an expert in biomedical engineering from the Faculty of Health Sciences, said people with multiple sclerosis benefit from regular exercise, but the progression of the disease meant many people gradually lose their ability to walk and stay active.

"Inactivity isn't good for any of us, but for people with MS it exacerbates health problems and can put them at greater risk of conditions like diabetes and cardiovascular disease," Dr Fornusek said.

The research team has a long history in world-leading research in electrical stimulation exercise and for this study adapted a bike they previously developed for people with spinal cord injuries. They are now undertaking testing to assess the benefits that can be gained for those with advanced multiple sclerosis.

Dr Fornusek said early trials show a lot of promise and the researchers were eager to see just how effective the exercise treatment could be.

"I'm confident we can improve the condition of people's legs and make tasks like transitioning to and from a wheelchair easier which is great. But I'm also keen to know if this exercise can improve the immune function and ultimately slow the progression of MS," he said.

The study is funded by a grant from MS Research Australia. Chief Executive Officer Dr Matthew Miles said the project highlights the importance of researchers continuing to seek new and innovative treatments for people in the advanced stages of the disease.

"This study has the potential to make a real difference to the quality of life for many people currently living with severe multiple sclerosis," Dr Miles said.

Source: HealthCanal (09/03/15)

Patients want full disclosure(06/03/15)

Individuals with multiple sclerosis want to know what’s going on behind closed doors concerning drug research, according to a study published in the Multiple Sclerosis Journal. The study shows MS patients want full disclosure concerning the financial relationship between the doctors and the drug companies in pharmaceutical industry-sponsored clinical trials (ISCTs) before they will agree to participate in such research.

Andrew Solomon, MD, a neurologist and MS specialist at the University of Vermont, and his colleagues from several other universities and medical centers, came to this conclusion after reviewing the responses on an anonymous survey completed by 522 individuals with multiple sclerosis.

Participation in clinical trials has the potential to provide benefits for the subjects as well as other current and future patients, along with yielding critical information for the investigators. However, when there are financial relationships between physicians and pharmaceutical companies involved in such research, red flags are raised about bias and the validity of the findings.

When agreeing to participate in pharmaceutical industry-sponsored clinical trials (as well as other types of clinical trials), patients are provided with information about the study, including its risks, in an informed consent document, which needs to be signed before participating in the research. Currently, however, patients do not see information concerning potential financial conflicts of interest regarding the participating physicians, such as monies generated by the trial or fees given to the doctors for consulting services or speaking engagements.

According to Solomon, he and his associates decided to conduct this study because “direct industry financial support of physicians, physician practices, and academic departments involved in MS therapy-related multicenter ISCTs are an infrequently acknowledged source of potential physician conflict of interest,” and they wanted to know how individuals with multiple sclerosis felt about this topic.

The authors learned that most of the surveyed individuals with multiple sclerosis believed that it was important for doctor-pharmaceutical company relationships to be disclosed. Respondents also rated monies paid toward the principal investigator’s salary as the most important thing they wanted to know about the physician-drug industry financial relationships.

Solomon and his team, who noted that “avoidance or minimization of potential conflicts of interest is the goal,” also stated that more research is needed on this issue.

Source: EmaxHealth 2015 (06/03/15)

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Survey highlights need for pain treatment information(05/03/15)

A new survey, conducted by Pain UK and St. Jude Medical, has found that although 66 per cent of people see their GP for chronic pain, the majority do not see a specialist or visit a pain clinic.

Almost ten million people in the UK suffer from chronic pain, according to Pain UK, which has a major impact on quality of life and day to day activities, such as work.

However many of those people do not have their pain under control or know how to go about seeking the right treatment. The new survey interviewed 1,614 people (1,090 general respondents and 524 chronic pain sufferers), and found that although chronic pain is quite prevalent, there is a general lack of awareness about what chronic pain is and how it should be treated.

Chronic pain is defined as continuous, long-term pain lasting more than 12 weeks or pain that remains after discomfort would traditionally recede after trauma or surgery. However, recent survey results revealed only 30 per cent of people surveyed who do not suffer from chronic pain actually understand what chronic pain is and how long it lasts. Additionally, for those who do suffer from chronic pain, results indicate many do not seek treatment any further than visiting their GP. In fact, only 15 per cent of those surveyed who suffer from chronic pain have actually visited a pain clinic to receive proper treatment and there is a general lack of awareness about treatments other than ‘painkiller’ medication.

Antony Chuter, of Pain UK, said: “The results of this survey show there needs to be increased awareness throughout the UK about chronic pain and how it should be treated. As this survey demonstrates, many people who are in chronic pain in the UK seek treatment, but go no farther than their GP. Patients should be educated about the treatment options available and also when to see a specialist and GPs should refer patients to pain clinics when necessary.”

Dr Vivek Mehta, consultant pain physician, Barts Health NHS Trust, said: “The statistics uncovered in this survey are concerning and a definite indication that awareness must be increased about chronic pain and the proper treatment for it. Although people believe that chronic pain is an actual condition, many are unaware of the treatment options and are living with a condition that has a profound negative impact on their quality of life. Aside from medication, there are numerous types of treatment available for people living with chronic pain, particularly failed back surgery, such as spinal cord stimulation, which works by implanting a “pacemaker” or a form of pulse generator that stimulates the nerves electronically in order to control the pain, and research is showing it to be an effective treatment in reducing patient’s pain. However, people across the UK are not accessing these types of treatment.”

Source: Pain UK (05/03/15)

Businesses missing out on £1.8bn a month(05/03/15)

A report released today by the Extra Costs Commission led by disability charity Scope has found that 75 per cent of disabled people and their families have walked away from a UK business due to poor service.

Drawing upon research conducted by Business Disability Forum (BDF) in 2006 on the income lost by businesses that fail to make goods and services accessible to disabled people, the Commission surveyed over 2,000 disabled people to find businesses are losing an estimated £1.8bn a month by ignoring the needs of disabled customers.

Three out of four people reported they and families moved spending away from businesses including supermarkets, banks, utilities, restaurants and transport companies as a result of poor service and lack of disability awareness.

A UK business membership organisation working with large private and public businesses that account for nearly 20 per cent of the UK workforce, BDF welcomed the report, which they say adds to a growing business case for improving accessibility and usability of products and services for disabled people.

George Selvanera, Director of Policy, Services & Communications at BDF, said: “The findings of the Commission's report are a call to action for business to seek out new ways of improving the customer experience for disabled people. The rapid ageing of the UK population, growing numbers of older and disabled people and changing technology make the case for business investing in improving accessibility more and more compelling.

“At BDF, we know it is not all bad news. Companies such as Barclays Bank, Enterprise Rent-A-Car, Sainsbury’s, BT and others are leading the way in inclusive design and improving the disabled and older customer experience. There is more to do definitely, but there is learning from some of the best.”

Warren Buckley, Chair of BDF, said: “The opportunities are there for businesses to grasp. We work with those that are already supplying excellent customer service, and this reports sets out how they can get even better at supplying of goods and services to disabled people.

“The Government value the purple pound at over £200bn. Businesses that improve how they work with disabled consumers will have an advantage over their competitors.”

Source: Business Disability Forum (05/03/15)

Genetic risk factor uncovered(05/03/15)

Researchers at the University of Illinois at Chicago have identified a genetic variation that in women significantly increases their risk of developing multiple sclerosis. The report is published in the journal ASN Neuro.

The variant occurs almost twice as often among women with MS as in women without the disease, making it "one of the strongest genetic risk factors for MS discovered to date," said senior author Doug Feinstein, professor of anesthesiology at UIC and research biologist at the Jesse Brown VA Medical Center.

Feinstein and his colleagues were able to test three sisters among a group of five siblings between the ages of 23 and 26, all diagnosed with MS. They found the variant in all three they tested.

What they found was a genetic change known as a single nucleotide polymorphism, or SNP - a change in a single base-pair of the DNA - in a gene called STK11, which plays a role in tumor suppression and is believed to have several roles in brain function.

Genetic factors are known to influence the risk of developing MS. The UIC researchers were led to this variant thanks to a woman participating in another study at UIC. In a casual conversation, the woman told study coordinator Anne Boullerne that she and her four siblings - three sisters, including twins, and a brother - all had multiple sclerosis.

"This is an extremely rare occurrence," said Boullerne, who is research assistant professor of anesthesiology and lead author on the paper. She said she could find no published studies with five siblings with multiple sclerosis.

"I was immediately interested in the possibility of a genetic study of the family because all five siblings - an entire generation - are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease."

The woman also described among her sisters and the women on her mother's side of the family a prevalence of diseases associated with Peutz-Jeghers syndrome, a rare genetic disorder caused by mutations in the STK11 gene and characterized by an increased risk for certain cancers, including breast, ovary and colon cancers.

A literature search by Feinstein uncovered an article that described how mice with a disabled STK11 gene had a higher incidence of loss of myelin from the nerves of the central nervous system - a defining characteristic of MS.

The woman consented to a complete DNA-sequencing of her genome. Boullerne took a close look at the STK11 gene, where she discovered the SNP. She next obtained consent to sequence the genomes of two of the woman's sisters and found they also carried the same SNP.

To determine if the SNP could be a contributing factor to the siblings' multiple sclerosis, the researchers screened DNA samples from 1,400 people - 750 with MS and 650 without - provided by Jorge Oksenberg at the University of California, San Francisco, who is a leading expert on the genetics of MS. They found that the SNP was 1.7 times as prevalent in women with MS as in women without the disease, making it one of the highest known genetic risk factors for MS.

Based on their analysis, the researchers estimate that the STK11 SNP is present in about 7 percent of the general population. But because far fewer people develop MS, other genetic or non-genetic factors must play a role in the development of the disease, Feinstein said.

Feinstein and Boullerne plan to continue their hunt for other genetic factors that may contribute to MS among the five siblings and possibly their parents. They will also investigate the function of the STK11 gene in the lab, which could reveal molecular pathways involved in multiple sclerosis.

Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (05/03/15)

FDA-approved drug ‘boosts myelin synthesis’(02/03/15)

The Journal of Neuroscience is reporting that a University at Buffalo researcher has discovered a way to keep remyelination going, using a drug that's already on the market.

According to scientists, there is a brief period after the myelin sheath has been attacked and damaged when it is able to repair itself, but this doesn’t last and the damage deteriorates further as someone with MS ages and their condition progresses.

“We have identified a new drug target that promotes stem cell therapy for myelin-based conditions such as MS,” says lead author Fraser J. Sim, PhD, assistant professor in the Department of Pharmacology and Toxicology in the University at Buffalo School of Medicine and Biomedical Sciences.

The study shows it is possible to boost myelination by targeting human oligodendrocyte progenitor cells with solifenacin, an anti-muscarinic drug that currently is approved and marketed to treat overactive bladder.

“Our hypothesis is that in MS, the oligodendrocyte progenitor cells seem to get stuck,” Sim explains. “When these cells don't mature properly, they don't differentiate into myelinating oligodendrocytes.”

In the new study, the approach Sim and his colleagues took was to first characterise the molecular pathways that govern the differentiation of human oligodendrocyte progenitor cells, and then identify drug candidates that would promote differentiation and myelin production.

They found that when a muscarinic type 3 receptor on human oligodendrocyte progenitor cells was activated, differentiation was completely blocked.

“So we thought, if we had something that blocks instead of activates this receptor, could we boost differentiation?” said Fraser. To do that, the researchers turned to solifenacin, the anti-muscarinic drug for overactive bladder; the bladder muscle contains several muscarinic receptors.

“We were excited about this because solifenacin is an approved drug that's already on the market,” said Sim.

To test whether the drug could boost myelin synthesis, the researchers transplanted human oligodendrocyte progenitor cells into mice that could not make myelin. The result was increased differentiation and myelin synthesis from the transplanted human cells.

However, Sim and his colleagues needed a functional endpoint, a way to know that the myelin being made was being translated into improved behaviour or function.

So Sim teamed up with Richard J. Salvi, PhD, SUNY Distinguished Professor in the Department of Communicative Disorders and Sciences, and director of UB's Center for Hearing and Deafness.

Together, they determined that an auditory brainstem response, which records brain wave activity in response to sounds, would be appropriate.

Sim said that it takes a certain amount of time for a signal to go from the ear to the front of the brain: “So in the readout, you get waves that should have a certain time pattern. When there isn't enough myelin, the signalling slows down. And if you add myelin, you should see the signals speed up.”

The tests showed improvement in the response to auditory signals in animals transplanted with the human oligodendrocyte progenitor cells treated with solifenacin.

“We have identified a way to improve human myelination,” said Sim.

The promising results have prompted Sim and his colleagues to seek funding for a small human trial. The study results are all preclinical and no human testing has been done yet.

The current study was funded by America’s National Multiple Sclerosis Society, the Kalec Multiple Sclerosis Foundation and the Empire State Stem Cell Fund.

In addition to Sim and Salvi, other co-authors are Kavitha Abiraman, Suyog U. Pol, Melanie A. O'Bara, Guang-Di Chen, Zainab Khaku, Jing Wang, David Thorn, Bansi H. Vedia, Exinne C. Ekwegbalu and Jun-Xu Li.

The new study adds to Sim's body of research on stem cells and myelination, which previously determined that a critical phase of remyelination fades with age.

Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (02/03/15)

‘Miracle’ stem cell therapy reverses multiple sclerosis(02/03/15)

A pioneering new stem cell treatment is allowing people with multiple sclerosis to walk, run and even dance again, in results branded ‘miraculous’ by doctors.

Patients who have been wheelchair-bound for 10 years have regained the use of their legs in the groundbreaking therapy, while others who were blind can now see again.

The treatment is the first to ‘reverse’ the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.

The two dozen patients who are taking part in the trials at the Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London, have effectively had their immune systems ‘rebooted’.

Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.

In the new treatment, specialists use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.

Stem cells are so effective because they can become any cell in the body based on their environment.

"Since we started treating patients three years ago, some of the results we have seen have been miraculous," Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, told The Sunday Times.

"This is not a word I would use lightly, but we have seen profound neurological improvements."

During the treatment, the patient's stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.

The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.

Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.

Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two, but she claims the new treatment has transformed her life.

“It worked wonders,” she said. “I remember being in the hospital... after three weeks, I called my mum and said: 'I can stand'. We were all crying.

"I can run a little bit, I can dance. I love dancing, it is silly but I do. I enjoy walking my daughter around the park in her pram. It is a miracle but I can do it all."

However specialists warn that patients need to be fit to benefit from the new treatment.

"This is not a treatment that is suitable for everybody because it is very aggressive and patients need to be quite fit to withstand the effects of the chemotherapy," warned Prof Sharrack.

Charities welcomed the research but also urged caution.

Dr Sorrel Bickley, Research Communications Manager at the MS Society said: “This new study reports very encouraging findings, which add to a growing body of research into stem cell transplantation in MS. However, there are limitations to how we can interpret these results because there was no control group used, which means we can’t be sure the results are robust.

"Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer term follow up data.

“New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."

The research was published in the Journal of the American Medical Association.

Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (02/03/15)

MS-UK launches live web chat service to support anyone affected by multiple sclerosis after seeing a 23% increase in contact(02/03/15)

MS-UK, the national charity supporting anyone affected by multiple sclerosis to make the most of today, has launched a live web chat feature on its website at www.ms-uk.org/livewebchat.

MS-UK has launched the new web chat service to support more people affected by MS. Between 2013 and 2014, the charity experienced a 23% increase in the amount of people who use the MS-UK Helpline. In January 2015 the MS-UK Helpline supported 32% more people compared to January 2014.

Amy Woolf, CEO of MS-UK, says ‘By launching the live web chat service, we hope to offer people another channel to connect with trained MS Advisors. Not everybody likes talking on the telephone, but they still want an instant response to their concerns. The growth we have seen in the past 12 months of people wanting information and support about multiple sclerosis tells us we’re doing the right thing.’

Since 1993, MS-UK has offered information and support to anyone affected by multiple sclerosis via telephone. The MS-UK Helpline is confidential, unbiased and completely free.

About MS-UK

At MS-UK we are dedicated to giving support and information to anyone affected by MS. We offer a range of services including our Helpline, publishing New Pathways magazine and access to our Wellness Studio at Josephs Court, MS-UK Centre of Excellence.

Find out more about MS-UK online at www.ms-uk.org

Source: MS-UK (02/03/15)

Studies indicate drinking coffee ‘may lower risk of MS’(27/02/15)

People who drink four to six cups of coffee a day may be less likely to get multiple sclerosis, US and Swedish researchers say.

While caffeine intake has been associated with a reduced risk of Parkinson's and Alzheimer's diseases, the findings of the research show the same could apply to MS.

“Our study shows coffee intake may also protect against MS, supporting the idea the drug may have protective effects for the brain,” said lead author Ellen Mowry of Johns Hopkins University School of Medicine.

The findings of twin US and Swedish studies compared more than 1,000 MS patients with a similar number of healthy people.

Researchers tracked how much coffee the subjects drank in the one, five and 10 years before symptoms began for those affected by MS.

After accounting for other factors such as age, sex, smoking, body mass index and sun exposure, the Swedish study found “compared to people who drank at least six cups of coffee a day during the year before symptoms appeared, those who did not drink coffee had about a 1½ times increased risk of developing MS”.

Similar protective effects were seen among those who drank lots of coffee five to 10 years before symptoms appeared.

The US study found “people who didn't drink coffee were also about 1½ times more likely to develop the disease than those who drank four or more cups of coffee per day in the year before symptoms started to develop”.

More research is needed to determine if caffeine has any impact on relapse or long-term disability due to MS.

Source: The Sydney Morning Herald © 2015 Fairfax Media (27/02/15)

Cinnamon can reduce symptoms of multiple sclerosis(25/02/15)

Oral feeding of cinnamon is capable of suppressing multiple sclerosis (MS) in mice models, according to research published in PLOS One.

Researchers from the Rush University Medical Center in Chicago examined the effects of various household spices on mice models of MS, in accordance with a $750,000 grant they were awarded by the National Institutes of Health in 2011. The mice were introduced to the model of MS, called experimental allergic encephalomyelitis (EAE) in mice, and were randomly placed on a scale from 0 = no disease to 5 = moribund. The cinnamon was introduced as a powder in 0.5 percent methylcellulose (MC) and EAE mice were given 100 µL cinnamon mixed MC powder once daily using a needle. After an observation period of 14 days post immunisation (dpi), 5 mice per each group were anesthetized and their spinal cords were evaluated for inflammation.

Ceylon cinnamon (Cinnamonum verum), the researchers found, was much more pure than Chinese cinnamon (Cinnamonum cassia), and so it was used in the study. Both are widely available for sale in the United States, the authors commented. Cinnamon, the researchers continued, has a long history of being used medicinally, including for treatments of arthritis, coughing, hoarseness, sore throats, and the like.

Less than half (40 percent) of mice developed EAE, and the EAE mice were treated with different doses of cinnamon powder from 8 dpi. Cinnamon significantly inhibited clinical symptoms, and no decrease in disease incidence was observed at a dose of 25 mg/kg body wt/d. At an increased dose of 100 mg/kg body wt/d, there was a very significant inhibition of clinical symptoms accompanied by a reduction in disease incidence.

“These results clearly demonstrate that cinnamon can ameliorate the ongoing relapsing remitting EAE when administered either early (at the onset of acute phase) or late (at the onset of relapsing disease),” the researchers described an additional result of the study.

The blood brain barrier (BBB) and blood spinal cord barrier (BSB) were also preserved after the treatment of cinnamon in transgenic mice. The investigators used infrared dye in EAE mice and tracked its spread, noting that the dye was strongly inhibited in mice who received the cinnamon treatment. In a similar analysis, the researchers discovered that the cinnamon treatment inhibited infiltration of mononuclear cells, inflammation, and demyelination in the spinal cord of EAE mice.

“These results highlight a novel immunomodulatory role of cinnamon and suggest that this widely-used spice may be explored for therapeutic intervention in MS,” the researchers concluded.

In July 2014, Rush similarly announced that cinnamon can also slow the effects of Parkinson’s Disease as well, citing the effects cinnamon has on the body once it is metabolised.

Source: MD All Specialities Copyright 2015 MJH Healthcare Holdings, LLC (25/02/15)

Study may explain beneficial effects of marijuana on people with multiple sclerosis(24/02/15)

Researchers in Spain have conducted a landmark study to shed light on how marijuana reduces the activity of motor neurons that lead to symptoms such as muscle weakness in people with MS.

Researchers at the University of Cadiz, led by Professor Bernardo Moreno, used synthetic analogues of the psychoactive compounds of marijuana to see how they affected motor neurons.

They looked, in particular, at movements of the tongue and how they responded to the drug.

'During the investigation, we used an animal model in which we studied the alterations produced by synthetic cannabinoids on the activity of the motor neurons,' the researchers wrote.

'In doing so, we discovered that these psychoactive compounds inhibit the information that reaches these neurons via the synapses.

'In other words, cannabinoids hinder the transmission of information between neurons.'

All of this could lead to problems speaking, breathing and swallowing food.

But the same reaction could also explain the beneficial effects that marijuana has on people with neurodegenerative diseases such as multiple sclerosis.

The scientists say that by reducing motor neuron activity, people with multiple sclerosis may have temporary relief from their symptoms.

Source: Daily Mail Online © Associated Newspapers Ltd 2015 (24/02/15)

Spinal Cord alteration in multiple sclerosis could lead to new therapeutic target(23/02/15)

A recent study led by researchers at the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, revealed a promising new method for MS treatment. The study was published in the journal Annals of Clinical and Translational Neurology and is entitled “Blocking GluR2–GAPDH ameliorates experimental autoimmune encephalomyelitis.”

MS is a progressive, immune-mediated disorder in which the body’s own immune system attacks the central nervous system (brain and spinal cord nerves). The exact causes for MS are not clear but the fact that the immune system is involved makes it a target for current therapies that address immune system responses. While the medications used in these therapies are not curative, they can help relieve the disease symptoms and slow its progression.

Researchers have identified a previously unknown spinal cord alteration linked to MS related to a protein called GAPDH (glyceraldehyde 3-phosphate dehydrogenase, a protein important in glucose metabolism) and a specific cell receptor for the glutamate neurotransmitter (the major excitatory neurotransmitter in the brain, critical for normal brain function). GAPDH was found to interact with this glutamate receptor, called the AMPA receptor, at higher levels in post mortem spinal cord tissues of MS patients and also in MS animal models. The AMPA receptor has been previously suggested as being able to mediate the cytotoxicity linked to the loss of neurons. Researchers therefore hypothesized that blocking AMPA-GAPDH interactions could be therapeutic for MS.

“We’ve identified a new biological target for MS therapy,” said the study’s senior author Dr. Fang Liu in a news release. The team discovered an approach to changing this alteration in order to stop nerve cell damage and also improve motor problems usually linked to the disorder. They developed a new peptide (a small piece of protein) to block the interaction between GAPDH and the AMPA receptor, more specifically GAPDH -GluR2 subunit of the AMPA receptor, and tested it in MS animal models.

“We found that our peptide disrupted this linkage, and led to major improvements in neurological functioning,” explained Dr. Liu. Mice treated with the peptide had their motor function significantly improved and a lower rate of neuron death along with myelin restoration, the protective coating of neurons important for the normal transmission of nerve impulses. More importantly, the peptide developed was found to be different from drugs targeting the glutamate system as it did not directly suppress the immune response of the body, which is a common side effect of many glutamate drugs.

The team believes that the GluR2-GAPDH complex could be a novel target for the development of new types of MS therapies that exploit a different mechanism from those currently used in treatments. “Our priority now would be to extend this research and determine how this discovery can be translated into treatment for patients,” concluded Dr. Liu.

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (23/02/15)

Study on immune response in MS targets new therapeutic approach(20/02/15)

A study published by a team of investigators at the University of Tokyo’s Institute of Medical Science and Osaka University’s Graduate School of Engineering has presented new evidence demonstrating how Toll-like receptor 9 (TLR9) binds to pathogenic DNA, turning on the functions of the innate immune system. This novel discovery is important for the design of new therapeutic drugs for autoimmune diseases, such as multiple sclerosis (MS), targeting TLR9. The study was published in the new issue of Nature.

Toll-Like Receptors (TLRs) play a critical role in the early innate immune (non-specific first line of defense against pathogens) response to invading bacteria, viruses, and other foreign agents and are also involved in sensing the body’s internal alarm system to help activate other important components of its immune defenses. TLR9 detects the alarm system by recognizing a DNA sequence called Cytosine-phosphate-Guanine dinucleotide (CpG), a pattern that is specific to bacteria and viruses. This induces the release of interferon (IFN) and initiates the inflammatory response process. For autoimmune disease such as MS, studies have shown that TLRs and the release of IFN play a major role in the initiation of disease, triggering of relapses and regulation of damage.

Unfortunately, the exact structure of TLR9 and how it functions remained unknown, inhibiting advancement of treatments that specifically targeted these receptors. This study conducted by Professor Toshiyuki Shimizu PhD’s research group used crystallographic (molecular structure) data to evaluate TLR9’s ring-shaped form in three crucial states: as a free protein, bound to an inhibitor DNA, and bound to an agonist DNA. In the first two cases, TLR9 exists as a single ring, but when it binds to an agonist, like a DNA segment containing the CpG motif, two of its rings are bound together and form a dimer (chemical structure formed from two similar sub-units) that shares two DNA molecules.

In a statement explaining the importance of the study findings, Professor Shimizu said, “TLR9 is a promising drug target for treating viral infections, cancer, autoimmune diseases, and so on, so researchers have been trying to elucidate structurally how TLR9 recognizes pathogenic DNA ever since it was discovered more than a decade ago. This work represents a big step forward for drug development targeting TLR9, and also for our understanding of nucleic acid sensing by TLR9. TLRs have received significant attention due to their critical roles in the innate immune system, and our group has been focusing on the structural study of TLRs for many years. We believe that a precise understanding of TLR function should come from its visualization by structural analyses. Actually, we were quite surprised at the result of this study: the two DNA molecules, agonist and inhibitor, bound to completely different sites on TLR9, and the DNA molecules themselves had completely different structures, both of which we could never have predicted.”

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (20/02/15)

Detailed map of brain reveals seven unknown cell types(20/02/15)

Due to its complex nature, scientists have only really been unravelling the mysteries of the brain over the last few decades, and now researchers have discovered that the brains of mice contain at least seven unknown types of cells, including a nerve cell.

These findings could shed light on conditions such as multiple sclerosis.

Using a process called single cell sequencing, scientists at the Karolinska Institute in Sweden produced a detailed map of brain cell types and the genes active within them.

It is the first time the method has been used on such a large scale and on such a complex tissue.

Researchers studied more than 3,000 cells, one at a time, to identify a number of previously unknown types.

‘If you compare the brain to a fruit salad, you could say that previous methods were like running the fruit through a blender and seeing what colour juice you got from different parts of the brain,’ said Sten Linnarsson, senior researcher at the Department of Medical Biochemistry and Biophysics.

‘But in recent years we've developed much more sensitive methods of analysis that allow us to see which genes are active in individual cells.

‘This is like taking pieces of the fruit salad, examining them one by one and then sorting them into piles to see how many different kinds of fruit it contains, what they're made up of and how they interrelate.’

After the scientist analysed the 3,000 cells from the cerebral cortex in mice, they compared which of the 20,000 genes were active in each one, enabling them to sort the cells into virtual piles.

They identified 47 different kinds of cell, including a large proportion of specialised neurons, as well as blood vessel cells and glial cells, which take care of waste products, protect against infection and supply nerve cells with nutrients.

Then, they identified unknown cell types, including a nerve cell in the outermost layer of the cortex plus six different types of oligodendrocyte.

These are cells that form the electrically insulating myelin sheath around the nerve cells.

The study, published in the journal Science, could shed more light on things that affect the myelin.

Co-leader of the study, Jens Hjerling-Leffler, said: ‘We have created a much more detailed map of the cells of the brain that describes each cell type in detail and shows which genes are active in it.

‘This gives science a new tool for studying these cell types in disease models and helps us to understand better how brain cell respond to disease and injury.’

Source: Daily Mail Online © Associated Newspapers Ltd 2015 (20/02/15)

People with multiple sclerosis may have lower levels of key nutrients(20/02/15)

Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a new study released today that will be presented at the American Academy of Neurology's 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.

For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18-60 and with body mass index of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.

On average, the women who had MS had lower levels of five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin and quercetin. For food folate, the women with MS had average intake of 244 micrograms (mcg), while the healthy women had an average intake of 321 mcg. The recommended daily allowance is 400 mcg. For magnesium, the women with MS had average intake of 254 milligrams (mg), while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.

"Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS," said study author Sandra D. Cassard, ScD, with John Hopkins University in Baltimore, MD. "Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear."

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS).

Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (20/02/15)

Early research shows results for ‘vaccine’ (18/02/15)

In April 2010, sipuleucel-T (Provenge) became the first dendritic cell vaccine in cancer treatment to be approved by the US Food and Drug Administration (FDA), and the agent is now used in the treatment of metastatic castration-resistant prostate cancer. Insights gleaned from this research are now being applied in the study of a potential vaccine for multiple sclerosis (MS) treatment and prevention.

“We discovered DC-ASGPR, one of the receptors expressed on human dendritic cells, has novel functions to promote antigen-specific regulatory T cells that can efficiently suppress inflammatory responses,” said principal investigator SangKon Oh, PhD, from the Baylor Institute for Immunology Research, in a press release. “This prompted us to test our discovery in autoimmune diseases where antigens are known.”

Traditional treatments for MS may trigger immune system–related side effects and adversely affect the immune system even though they demonstrate efficacy. Oh launched lab research 3 years ago along with colleagues Gerard Zurawski, PhD, and Ted Phillips, MD, PhD, using a significantly different approach.

“Oh’s approach is a very unique effort that would harness one’s own immune system to suppress MS in an auto antigen–specific manner without disrupting other aspects of normal immunity,” said Phillips, a neurologist whose work has focused on MS for more than three decades. Results have been positive, according to Oh, who said they are hopeful this study can enter a phase I clinical trial within the next three years. Researchers will also apply these findings to future studies about dendritic cell vaccines, including a planned research effort for type 1 diabetes mellitus.

“We need new treatments that, while highly efficacious, also minimally adversely impact the individual’s immune system,” Phillips said.

Source: HCPLive Copyright HCPLive 2006-2015 Intellisphere, LLC (18/02/15)

New molecule may improve treatments for inflammatory diseases(18/02/15)

A team of scientists have uncovered a molecule that fights one of the main causes of inflammatory diseases and could be the key to improved treatments for diseases like Alzheimer's, arthritis and multiple sclerosis. The research team, led by Trinity and the University of Queensland Australia, showed the molecule, MCC950, could suppress the key activator in inflammatory diseases, NLRP3. The finding also confirms that inflammatory diseases all share a common process, even though the part of the body becoming inflamed might differ.

Researcher Luke O'Neill said drugs like aspirin or steroids can work in several diseases, but can have side effects or be ineffective, and what they have found is a potentially transformative medicine, which targets what appears to be the common disease-causing process in a myriad of inflammatory diseases. There is huge interest in NLRP3, both among medical researchers and pharmaceutical companies, and they feel their work makes a significant contribution to the efforts to find new medicines to limit it. MCC950 can be administered orally and will be cheaper to produce than current protein-based treatments, which are given daily, weekly, or monthly by injection.

More importantly, the new molecule also remains in the body for a shorter duration, allowing clinicians to stop the anti-inflammatory action of the drug if the patient ever needed to switch their immune response back to 100 percent, in order to clear an infection. So far, the results have shown great promise for blocking multiple sclerosis in a model of the disease, as well as in sepsis where, in response to bacteria, potentially fatal blood poisoning occurs. However, the target for MCC950 is strongly implicated in diseases such as Alzheimer's disease, atherosclerosis, gout, Parkinson's disease and rheumatoid arthritis, which means it has the potential to treat all of these conditions. The study is published in medical journal Nature Medicine.

Source: dna © 2015 Diligent Media Corporation Ltd (18/02/15)

Uric acid correlated with multiple sclerosis disease activity(18/02/15)

In a study published in the journal Clinical Chemistry and Laboratory Medicine, investigators Moccia et al identified uric acid as a potential biomarker in the progression of multiple sclerosis-related disability.

Uric acid, which has activity as a natural scavenger of oxygen radicals, is present in the bloodstream as a breakdown product of purines (adenine and guanine). In animal studies, uric acid has been shown to have some potential as a treatment for MS. Results of these studies led investigators in the CCLM study to search for a relationship between MS severity and levels of uric acid. In the case-control study, using propensity score matching, investigators paired 362 patients with MS and 181 control individuals without MS.

To reduce variation between populations, investigators corrected data for patient age, gender, and kidney function. Upon regression analysis, investigators identified a significant association between low levels of serum uric acid among patients with MS compared with controls, with an R-squared value of 30.4 per cent and significance determined at a P value level of 1.4 per cent.

Longer disease duration was associated with a longer time from diagnosis and a higher Expanded Disability Status Scale (EDSS) score (P < .001, all comparisons). These findings suggest that uric acid levels may be a biomarker of MS disability and progression, even though previous studies suggest that uric acid may have a limited role as a disease marker and as a therapeutic target in MS.

For example, a 2006 analysis, published in the journal Clinical Neurology and Neurosurgery, found that uric acid levels did not change as a result of immunomodulatory or immunosuppressive drug treatment in patients with MS.

In addition, in the Association of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial, investigators administered a precursor of uric acid — inosine — to patients with MS in conjunction with interferon-beta over the course of two years. The results of this trial were negative, and uric acid did not have any additional benefit on disability outcomes versus interferon-beta alone.

Despite the negative result of the ASIIMS trial, antioxidative drugs may have a future in treatment of MS. However, uric acid may be a biomarker — not a treatment modality. Studying uric acid may help physicians predict the progression of MS in patients, although previous research indicates that uric acid levels do not predict response to treatment, and supplementation with uric acid does not alter the progression of disability in MS. Further study will be necessary to determine whether or not drugs that mimic the effects of uric acid are of any value.

Source: HCPLive Copyright HCPLive 2006-2013 Intellisphere, LLC (18/02/15)

Oral regimen ‘delays onset of MS’(17/02/15)

For the first time, an oral therapy has been proven to reduce the risk of developing clinically definite multiple sclerosis in patients with a clinically isolated syndrome. In a phase III trial published in the journal Lancet Neurology, Miller et al clarified the role of teriflunomide (Aubagio) in the treatment of early episodes of demyelinating symptoms suggestive of MS.

This randomized, double-blind, placebo-controlled study, known as the TOPIC study, evaluated the safety and efficacy of teriflunomide for patients between 18 and 55 years of age who had experienced their first instance of a clinically isolated syndrome in the 90 days prior to randomization in the trial. Each patient involved in the study was required to have at least 2 MRI-determined lesions (measured using T2-weighted MRI) at least 3 mm in diameter.

Investigators assessed the amount of time between the initial neurologic event and any new neurologic event — an event that would mark the transition from a clinically isolated syndrome to clinically definite MS (CDMS). Secondarily, investigators assessed MRI outcomes, including occurrence of new gadolinium-enhancing or T2 lesions. The study used an intent-to-treat design, but excluded from the study two patients who were randomized to receive teriflunomide but never received a dose of study medication.

Two different regimens of daily teriflunomide significantly reduced the risk of conversion to CDMS. The 7-mg dose reduced the risk of developing CDMS by 31.4 per cent, and the 14-mg dose reduced the risk of developing CDMS by 34.9 per cent.

Adverse events (AEs) occurring in the trial included increased liver enzyme levels, hair thinning, diarrhea, paresthesia, and upper respiratory tract infection. Each of these AEs occurred in at least 10 per cent of patients using teriflunomide, and occurred at a rate at least two percentage points higher than in patients receiving placebo.

Serious AEs included increased liver enzyme levels, which occurred in two per cent of each treatment group—including the placebo group.

The TOPIC study is the first to evaluate the efficacy of an oral treatment in reducing the risk of progression from a clinically isolated demyelinating syndrome to clinically definite MS.

Source: HCPLive Copyright HCPLive 2006-2013 Intellisphere, LLC (17/02/15)

Low CD8+ T cell counts found with MS drug Tecfidera(13/02/15)

A recent study found that patients taking dimethyl fumarate (Tecfidera) had low counts of CD8+ T cells, though their overall levels of lymphocytes were within the normal range. The findings suggest that doctors may want to monitor specific lymphocyte levels in addition to doing full blood cell counts.

In November 2014, Biogen Idec confirmed its first case of progressive multifocal leukoencephalopathy (PML), a rare brain infection, in a patient taking dimethyl fumarate (Tecfidera), and complications from the infection resulted in the patient’s death. The news sparked a warning from the U.S. Food and Drug Administration and concern from both patients and physicians about how to prevent another case of PML.

Research from the University of California, San Francisco (UCSF), may provide some insight on better monitoring techniques for patients taking dimethyl fumarate (DMF). In a paper published in Neuroimmunology & Neuroinflammation (Spencer et al., 2015), researchers followed 14 patients every three months for a year and examined levels of leukocyte and lymphocyte subsets including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD56+ natural killer cells.

They found that total leukocyte and lymphocyte levels diminished by the 6-month mark and that half the patients had leukocyte levels below the lower limit of normal. While the levels of all the cell subsets dropped over time, the researchers noted a particularly striking decrease in the level of CD8+ T cells, which are primarily involved in responding to viral infection.

PML develops from an opportunistic virus called the John Cunningham virus. DMF comes with a recommendation that physicians take blood cell counts of patients before starting on the drug and annually or as clinically necessary afterward. The safety precautions recommend that physicians consider interrupting treatment if lymphocyte counts decrease below 500 cells/μL in the blood and the low levels persist for six months. The label also says patients should stop taking DMF if any symptoms of PML occur, which include “clumsiness; progressive weakness; and visual, speech, and sometimes personality changes,” according to the National Institute of Neurological Disorders and Stroke. The symptoms of PML can also develop slowly over the course of weeks to months.

Typically, cell counts look at the major types of blood cells (red blood cells, lymphocytes, and leukocytes) but do not look at subsets. What the UCSF team found was that patients may have dangerously low levels of cell subsets, like CD8 cells, while still having total leukocyte and lymphocyte counts within the normal range.

“[CD8+ T cells] are the cells that are very important in antiviral immunity,” corresponding author Scott Zamvil, M.D., Ph.D., of UCSF told MSDF. Without the CD8+ T cells, the JC virus that leads to PML may be more able to infiltrate the body while the immune system has its guard down. But due to the small sample size and the relative short duration of the study, Zamvil said the results are not yet definitive. “So we need more investigation. These results are cautionary.”

Zamvil also said that the investigators did not take biopsies of the brain or lymph nodes, which may have different cell levels that could affect a patient’s susceptibility to or protection from PML. But due to the nature of the results, Zamvil told MSDF that he and his colleagues felt it important to get their data out there so that clinicians can make use of it.

Source: Multiple Sclerosis Discovert Forum Copyright © 2014 MGH and ACP (13/02/15)

New treatment for MS fatigue suggested(12/02/15)

The Multiple Sclerosis Journal has published the results of a study by researchers from Israel who measured the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue.

Fatigue is one of the most common and disabling symptoms of multiple sclerosis, occurring in up to 90 per cent of people with MS.

MS-related fatigue is not directly linked to depression or degree of neurological disability, and may occur first thing in the morning even if the patient has slept well.

At the moment, there is no medication approved specifically to treat MS-related fatigue. Amantadine was the first medication used to treat fatigue, although most studies have not shown evidence of benefit. Modafinil was studied recently, also showing inconsistent results.

Several non-drug interventions have also been proposed including aquatic exercise training, occupational therapy, and internet-based programs.

Combating MS-related fatigue is of importance to those affected by MS, as it interferes with daily living, work, family life and socialising.

In the study, 158 MS patients with significant fatigue received Alfacalcidol or a placebo.

The researchers found Alfacalcidol is a safe and effective treatment for fatigue among patients with MS.

These findings suggest that Alfacalcidol, a drug similar to vitamin D, should be considered a safe treatment option for MS-related fatigue.

Original Paper

Source: Multiple Sclerosis International Federation (12/02/15)

Research breathes new life into theory supporting possible viral etiology of multiple sclerosis(11/02/15)

Several clusters of multiple sclerosis cases have been identified around the world, some of which have occurred in association with exposure to infectious agents, while others have suggested an influence of environmental toxins, such as heavy metals.

Although MS is likely a result of multifactorial influences, there is some evidence that viruses play a role in the disease. For example, in the Faroe Islands, which lie northwest of Scotland and halfway between Iceland and Norway, native residents began to develop MS starting in 1943 after British occupation of the island during World War II. Although no virus was ever identified, John F. Kurtzke, MD, creator of the Kurtzke Expanded Disability Status Scale, said he believes the Faroe Island cluster suggests a viral etiology of MS.

In a scientific paper published in 2013 in the journal Brain, Kurzke wrote, “As of 1999, we had found 189 suspected cases, and we had agreed that 83 of them were examples of MS… There is no evidence that MS occurred among native-born resident Faroese before July 1943, when symptoms began in one patient… The abrupt onset indicates that the disorder had to have been introduced into the islands at a single time.”

In later research, Kurtzke, who is professor emeritus at Georgetown University in Washington, DC, identified similar patterns of MS incidence in Iceland and the Shetland-Orkney islands.4 Kurtzke and colleagues also examined the prevalence of MS in populations migrating from equatorial regions (where the prevalence of MS is low) to higher latitude regions (where the prevalence of MS is higher). From these studies, Kurtzke concluded that MS may be partly caused by a virus acquired before the age of 15 years, which may then lead to MS symptoms after a delay of 15 to 20 years.

Adding to the knowledge base developed by Kurtzke about the relationship between MS and viruses, Julian Gold, MBBS, MD, of the Albion Street Centre in Sydney, Australia, and colleagues studied the link between MS and human immunodeficiency virus (HIV). HIV and MS are both well-characterized conditions, although they rarely occur in the same patient.6 In 1996, Gold noticed that one of his patients who had both MS and HIV experienced a reduction in symptoms after starting antiretroviral therapy. Over 12 years of therapy, the patient continued to experience few symptoms of MS. Based on this case, Gold hypothesized that the antiretroviral medication, the immunosuppression associated with HIV, or both, might slow the progression of MS.

To evaluate the hypothesis, researchers in Denmark studied the incidence of MS in patients with HIV. Investigators followed 5018 patients with HIV over a median of 5.2 years and compared those results with a control population of 50,149 MS-free individuals who were followed for a median of 7.6 years.

Seven cases of MS were observed in patients with HIV, even though approximately 18 cases would be expected in a comparable group of patients without HIV. The relative risk of developing MS was significantly lower among patients with HIV, with new cases of MS occurring at more than one-third (38%; 95% confidence interval [CI]: 15%-79%) the rate observed in the general population.

In a secondary analysis, investigators analyzed MS cases that were identified in patients 1 year or more after they acquired HIV. A total of 3 such cases were identified. Although this number was smaller than the expected number of 13 cases of HIV that would be expected to occur in a similar population without HIV, the result was no longer statistically significant (hazard ratio: 0.25; 95% CI: 0.07-0.65). The lack of statistical significance may be a result of the small number of MS cases observed in patients with HIV.

According to Gold, who presented his research in MS at the Barts and London School of Medicine and Dentistry on MS Research Day in 2013, “As a result of these observations, we are now launching a unique clinical trial … the INSPIRE trial.” This trial will begin with a pilot phase in which patients with RRMS will receive raltegravir over a 3-month baseline period and a 3-month treatment period. Patients will be evaluated for the primary outcome of new gadolinium-enhancing lesions.7,8 Gold compares the pathophysiology of MS with a car lying in pieces: “It’s very complicated…all over the world there are researchers working on little bits to do with MS. Some are working on vitamin deficiencies, and others are working on Epstein-Barr virus (EBV), and others are working on hypoxia, but nobody has been able to put all these pieces together and drive it away.”

The pathophysiology of MS is very complex and the involvement of viruses is far from certain. For now, the use of antiviral agents in patients with MS should be limited to the clinical trials setting.

Source: HCP Live © HCP Live (11/02/15)

Scientists update recommendations on MS research(12/02/15)

Several renowned scientists working on multiple sclerosis (MS) recently joined forces to discuss and highlight the progress and knowledge gaps related to MS research, the prospects of finding a cure for the disease, and a strategy to reduce the burden the disease places on patients.

A series of articles was published by the researchers in the February issue of the Lancet Neurology journal and stress the need for better diagnosis and MS treatments.

Authors from different academic fields who share the same interest in MS research have outlined a state-of-the-art plan for MS investigation and updated information on what causes the disease to progress, its mechanisms, and the development of novel methods to conduct clinical trials.

The first article is focused on recent data concerning nervous system damage leading to progressive disability in MS, and calls for increased insight into the causes of MS disease progression. The authors Don Mahad from the University of Edinburgh, Bruce Trapp from the Cleveland Clinic, and Hans Lassmann from the Medical University of Vienna explained that progressive damage can be either caused by oxidative injury (derived from normal byproducts of bodily processes called free radicals) or by injuries to mitochondria, which are the energy-producing organelles inside cells.

In addition, the authors state that both type of injuries, believed to be initiated by MS attacks, are amplified due to alterations throughout patients’ lives. Even though there is an increased understanding about the mechanisms behind MS, there are still not enough models of the chronic stages of injuries related to the disease. 

Treating symptoms related to MS and rehabilitating patients with them requires the evaluation of new therapies in clinical trials. Anthony Feinstein from the University of Toronto, Jenny Freeman from Plymouth University, and Albert Lo from Brown University believe that overall there have been too few studies involving only people with progressive MS, and as a result there is a lack of disease-modifying therapies for progressive stages of the disease.

Additionally, Jeremy Chataway from University College London, along with Daniel Ontaneda and Robert Fox, both from the Cleveland Clinic, debate the problem of negative results from phase III trials to evaluate new therapies in progressive MS patients. The authors provide a series of lessons and strategies to improve results, such as applying improved clinical measures of effectiveness, better trial designs, and the use of advanced imaging tools and spinal fluid biomarkers to better understand treatment benefits.

Finally, Timothy Coetzee from the National MS Society, Paola Zaratin from the Italian MS Foundation, and MS blogger Trevis Gleason give insights on the need for research partnerships, regulatory innovations, and more sustained funding for research. They also evaluate the work of the international organization Progressive MS Alliance, which has recently opened a second request for research proposals, encouraging international research partnerships. The organization has been dedicated to funding and supporting research in order to improve the lives of MS patients.

“Every time a new treatment for RRMS comes on the market, it serves to remind people with progressive multiple sclerosis that they are still waiting,” stated Alan Thompson from the University College London in his article on new MS therapies. The authors believe it is crucial to understand what causes the development of progressive MS, as well as to innovate clinical trial design.

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (12/02/15)

Spinal cord and retinal measures independently relate to MS disability(12/02/15)

New research found statistically significant correlations between MRI measures of the spinal cord, optical coherence tomography measures of the retina, and clinical disability.

Two common categories of multiple sclerosis symptoms, visual and sensorimotor, are associated with lesions in the spinal cord (SC) and optic nerve. The symptoms also co-occur frequently in specific classes of demyelinating diseases such as neuromyelitis optica. Researchers from Johns Hopkins University recently tested for a relationship between the two central nervous system structures (Oh et al., 2015).

The team conducted MRI scans of the spinal cord and optical coherence tomography scans of the retinas of 11 healthy controls and 102 patients with MS: 66 relapsing-remitting and 36 progressive. They assessed the participants for visual acuity and sensorimotor dysfunction, and then looked for statistical associations between scans and clinical phenotype.

In a univariate analysis the investigators found several SC-related measures were associated with the peripapillary retinal nerve fiber layer (pRNFL). Incorporating those factors into a multivariate statistical model that controlled for age, sex, and prior optic neuritis, the team then analyzed SC cross-sectional area (SC-CSA), pRNFL, and brain parenchymal fraction . They found that SC-CSA and pRNFL independently correlated with multiple clinical measures. Specifically, both measures had statistically significant associations with low-contrast visual acuity, high-contrast visual acuity and vibration sensation threshold. Additionally, SC-CSA had a significant association with Expanded Disability Status Scale, but pRNFL did not associate with EDSS.

The study adds credence to the intuitive notion that MS has global effects on the central nervous system (CNS). Rather than causing damage in the brain alone, the disease affects all areas of the CNS and, as these data suggest, damage in the SC and optic nerve may be more closely associated with specific clinical symptoms of MS than with brain damage and atrophy.

But the study also had its limitations. The control group was rather small, and though 102 MS patients is a reasonable cohort size, the statistical power dwindles when they are examined by relapsing and progressive subgroups.

In the article, the authors suggest that in the future, SC and retinal scans may supplement brain scans to illuminate causes for specific variations in clinical disability. If their findings are validated, they went on to write, the approach would also better researchers’ understanding of the disease course and progression.

Source: Multiple Sclerosis Discovery Forum Copyright © 2014 MGH and ACP (12/02/15)

Stem cell treatment may cut new brain lesions in MS(12/02/15)

Multiple sclerosis patients who had autologous hematopoietic stem-cell transplantation had significantly fewer new lesions on MRI than those on mitoxantrone, Italian researchers have found.

In a randomized, controlled trial, CD34-positive hematopoietic cell transplant reduced the number of new T2 lesions by 79 per cent compared with mitoxantrone over a four-year study period, Giovanni Mancardi, MD, of the University of Genova in Italy, and colleagues reported in Neurology.

The therapy also reduced gadolinium-enhancing lesions and annualized relapse rate, but there was no difference in progression of disability, although the study was not powered to look at the latter finding, the researchers noted.

"More research is needed with larger numbers of patients who are randomized to receive either the stem-cell transplant or an approved therapy, but it's very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that are not responding well to standard treatments," Mancardi said in a statement.

The ASTIMS study enrolled 21 patients from seven centers in Italy and Spain from 2004 to 2009 who had relapsing-remitting or secondary progressive MS. They were randomized to intensive immunosuppression followed by either mitoxantrone or autologous hematopoietic stem-cell transplantation every month for 6 months.

The intensive immunosuppression regimen involved mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine arabinoside, etoposide, melphalan, and anti-thymocyte globulin.

The mean age at transplantation was 35.5 years, and the median Expanded Disability Status Scale (EDSS) score at baseline was 6.

ASTIMS was designed as a phase III study, but became a phase II trial with a primary laboratory endpoint -- the cumulative number of new T2 lesions 4 years after randomization -- "when it was clear that the number of enrolled patients was lower than expected," the researchers wrote.

Overall, Mancardi and colleagues found fewer T2 lesions in the stem-cell group than in the mitoxantrone group during follow-up at a median of 2.5 lesions versus a median of eight lesions.

This effect was evident in the first year and was sustained through four years of follow-up, they reported. It was also maintained in all sensitivity analyses. It also resulted in complete suppression of active inflammatory lesions as measured by gadolinium-enhancing lesions, with no stem-cell patients having new lesions compared with 56 per cent of those on mitoxantrone.

The annualized relapse rate was also lower for stem-cell patients. However, there was no significant difference in terms of progression of disability between groups, occurring in 48 per cent of the mitoxantrone group and 57 per cent of the stem-cell group, with no differences in EDSS changes at any point, the researchers said.

Mancardi and colleagues attributed this to the study being underpowered to look for this outcome.

In addition to this limitation, and the fact that the study was changed from phase III to phase II, it was also limited by its small number of cases and by a lack of data on quality of life and brain atrophy outcomes.

In an accompanying editorial, Paolo Muraro, MD, PhD, of Imperial College London, agreed that the lack of improvement in progression of disability was likely due to the study being underpowered.

Muraro also noted that mitoxantrone might not be the contemporary choice of comparator "having lost traction because of its cardiac toxicity and risk of lymphoma," although it was the most appropriate control treatment at the time the trial was started.

Given that stem-cell transplant isn't a licensed therapy for MS, more work is needed, Muraro said, noting that a phase III trial currently underway is likely to gain traction because the current study will "raise interest and catalyse activities to move forward with the new trial."

The study was supported by the Italian Multiple Sclerosis Foundation.

Mancardi disclosed relevant relationships with Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi, and Teva. Many co-authors disclosed multiple relevant relationships with industry including Biogen Idec, Novartis, Merk-Serono, Genzyme, Teva Pharmaceutical Industries, Genmab A/S, and Bayer Schering Pharma.

Muraro disclosed no relevant relationships with industry.

Source: MedPage Today © 2015 MedPage Today, LLC (12/02/15)

Alkermes reports positive data on multiple sclerosis drug ALKS 8700(11/02/15)

Alkermes plc has reported positive top-line data from a phase I study on its experimental MS drug, ALKS 8700. ALKS 8700 is a novel monomethyl fumarate (MMF) molecule being developed for the treatment of MS.

The three-part, randomized, double-blind phase I study was conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of several oral formulations of ALKS 8700 as compared to both placebo and active control groups in 104 healthy volunteers.

Data from the phase 1 study revealed that ALKS 8700 provided MMF exposures with less variability and improved gastrointestinal (GI) tolerability when compared to Tecfidera. Patients reported lower GI-related adverse events when treated with ALKS 8700 (8.3 per cent) as compared to Tecfidera (41.7 per cent). Moreover, the candidate was also found to be well tolerated during the course of the study.

Encouraged by the positive results from the phase I study, Alkermes plans to conduct a meeting with the FDA and move a twice-daily dose of ALKS 8700 into a pivotal development program this year.

Source: Zacks Copyright © 2015 Zacks Investment Research (11/02/15)

Gilenya may be best in MS patients failing initial treatment(11/02/15)

Switching multiple sclerosis patients with disease activity despite treatment with a first-line injectable to oral fingolimod (Gilenya) was associated with fewer relapses than switching them to another standard injectable, researchers have found.

In a study, patients on either interferons or glatiramer acetate (Copaxone) who were switched to fingolimod had a significantly lower mean annualized relapse rate than those who changed to another injectable immunomodulator, according to Tomas Kalincik, MD, PhD, of Royal Melbourne Hospital in Australia, and colleagues.

Patients in the study, reported online in JAMA Neurology, were switching medications following clinical relapse or disability progression while on the initial treatment.

In an accompanying editorial, Olaf Stuve, MD, PhD, of the University of Texas, and Diego Centonze, MD, PhD, of To Vergata University and Hospital in Rome, said the study adds to growing evidence that switching to newer agents like natalizumab (Tysabri) or fingolimod may be more effective.

Although it was an observational study, it assessed high-quality data and used appropriate propensity score matching to control for potential confounding factors, they wrote.

They noted, however, that the study's median follow-up of 13.1 months may be "too short to draw definite conclusions on the relapse rate."

Kalincik and colleagues conducted their matched retrospective analysis of data that was collected prospectively from MSBase, which collects data on MS patients in routine clinical care, from July 1996 to April 2014.

Patients with relapsing-remitting MS had been on a beta-interferon drug or glatiramer acetate for at least 6 months before making the change to another injectable (beta-interferon or glatiramer acetate) or to fingolimod because of clinical disease activity. They were then observed on the new medication for at least 3 months. Some of the patients initially taking a beta-interferon drug were switched to a different beta-interferon.

Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. Median follow-up was 13.1 months.

Kalincik and colleagues found that those switched to fingolimod not only had a lower mean annualized relapse rate but also a lower risk of first on-treatment relapse than those switched to another injectable immunomodulator.

Those changed to the oral drug also had a lower risk of disability progression and a higher rate of disability regression (HR 2.0, 95% CI 1.2-3.3, P=0.005), they reported.

They also had a lower rate of treatment discontinuation at 2 years.

The researchers noted that sensitivity analyses replicated in full the relapse and disability outcomes seen in the primary analysis. They did not, however, replicate the finding that switching to fingolimod improved treatment persistence, suggesting that this finding be interpreted with caution.

Kalincik and colleagues concluded that in the absence of randomized clinical trials, use of high-quality observational data provides an important tool for comparisons of drug effectiveness in a real-world setting.

In their editorial, Stuve and Centonze agreed that the quality of observational data in their study can provide "crucial information to support decision making relevant for MS management in real-world practice."

They said the results provide the first evidence that "switching to fingolimod is superior to switching to a second injectable immunomodulator with respect to disability outcomes, likely owing to the more efficient prevention of relapses associated with an incomplete recovery."

The results are in line with studies such as TRANSFORMS, one of the clinical trials leading up to fingolimod's approval, which found patients with active disease activity despite immunomodulatory therapy "may still have optimal disease control after switching to fingolimod."

In addition to the limitation of a short follow-up time, the study was also limited by lack of data on interferon-neutralizing antibodies, and because patients who were switched from one interferon preparation to another may not have served as true controls: "Most MS experts would not likely recommend this strategy because the agents are biochemically almost identical, and their mechanisms of action identical," they noted. The study, which was funded by fingolimod's manufacturer, also did not examine switches to natalizumab or newer oral agents.

Still, they concluded that evidence has accumulated that "escalating to the more effective medications natalizumab or fingolimod should be an early consideration for most patients with breakthrough disease. Switching to another injectable immunomodulator may still be considered in certain cases only."

The study was supported by Novartis, MSBase Foundation, Multiple Sclerosis Research Australia, National Health and Medical Research Council, and the Center for Research Excellence.

MSBase Foundation receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi.

The researchers disclosed financial relationships with Biogen Idec, Novartis, Genzyme, Merck Serono, Teva, Bayer Schering, Sanofi, Lundbeck, Bayer, Biologix, GSK, Roche, and bioCSL.

The editorialists disclosed financial relationships with Teva, Opexa, Merck Serono, Genzyme, Bayer Schering, Biogen Idec, Novartis, Almirall, GW Pharmaceuticals, Roche, and Mitsubishi.

Source: MedPage Today © 2015 MedPage Today, LLC (11/02/15)

Pathological progression of MS documented for the first time(11/02/15)

In a paper published in the journal Lancet Neurology, an international team of researchers from Edinburgh, Cleveland and Vienna, under the leadership of Hans Lassmann, Head of the Department of Neuroimmunology at the MedUni Vienna, has for the first time documented the pathological progress of multiple sclerosis from its early to late stage and also shown that inflammatory and neurodegenerative processes have a role to play.

Until now, there have been two approaches to categorising the condition: the first approach regards MS as a disease of the nervous system that is inflammatory throughout, with the inflammation also being responsible for the subsequent neurodegenerative damage. The second approach postulates that the condition ultimately progresses from an inflammatory condition into a neurodegenerative one. In their current paper however, the team of researchers has demonstrated that MS is comprised of both factors - and that the inflammatory process acts as a "driving force" from the onset right to the end, and that neurodegenerative processes also occur in the so-called progressive, late phase that damage the brain.

Lassmann said: "The inflammatory process, which can be treated effectively in the early stages, becomes less pronounced with age. However the neurodegenerative damage increases. This also explains why drugs that initially work well later lose their effectiveness."

In the later stages of the condition, "amplification mechanisms" are triggered: the damage becomes amplified - and in a "self-contained" cycle that continues to cause destruction. The neurodegenerative damage in the brain activates microglial cells that also drive the disease forward, along with the formation of oxygen radicals that destroy lipids and proteins in the brain. At the same time, damage occurs to the mitochondria, which act as the power plants and energy providers to cells in the brain. This - coupled with normal brain ageing and the associated deposition of iron - also causes further damage.

New approaches to treatment could be developed based on the new discoveries about all of these mechanisms, say the researchers. "There are two routes", says Lassmann. "First, drugs could be developed that have an anti-inflammatory effect in the brain too, not just suppressing the defence response in the blood and lymphatic organs. Secondly, neuroprotective treatments could be developed that block the amplification mechanisms and damage to the mitochondria, thereby preventing consequential damage."

Clinical studies involving a number of potentially useful medications are already under way on the basis of this new data. The results will not be known for at least five years.

Lassmann said: "I firmly believe that in the foreseeable future, so within the next five to ten years, we will be successful in fighting the amplification mechanisms and slowing down the progressive phase further."

Source: Health Canal (11/02/15)

Patients trial drug containing teenage acne bacteria(09/02/15)

A new drug for the treatment of multiple sclerosis is being trialled in Australia.

The potential new treatment is derived from the same bacteria that causes acne in teenagers and aims to stimulate responses in the immune system. Principal investigator Dr Bob Soh, from the Nucleus Network in Melbourne, said there are currently no effective treatments for secondary progressive MS. Already eight people in Victoria are signed up to the phase 2B trial of the drug MIS416, reports the Herald Sun, which will determine if the drug can improve their symptoms.

Unlike other drugs that use a man-made version of the substance, MIS416 takes the bacteria and puts it through a manufacturing process that leaves behind just the microparticle required to elicit the immune reaction against MS.

Trial participants are given weekly infusions of the drug or a placebo.

Dr Soh said that at the end of a 52-week trial period scientists would “unblind the trial” giving those who received the placebo the option of receiving the medication.

Trials of the drug in New Zealand have shown modest improvements in symptoms.

Stephen Mudgway, 51, has been on the drug for three years. He said: “Before I was on the drug I was sleeping for 18 hours a day, but it has given me my life back.”

In addition to the reduction in fatigue, the father of three has noticed improvements in his hand/eye coordination, cognition and he can stand for longer periods of time.

Results of the trial, which has also just been opened to Queenslanders, are expected to be known within two years.

Nucleus Network is one of Australia’s leading clinical research organisations for the conduct of early-phase clinical trials for the development of new medicines.

Source: Herald Sun Copyright News Corp 2015 (09/02/15)

Studying vision impairments in multiple sclerosis(09/02/15)

Vision impairments due to multiple sclerosis is common but an under studied area, according to a report published in Brain. Researchers from both the United States and the United Kingdom reported on an international meeting of investigators aiming to develop and study visual outcomes in MS. The Dublin meeting was attended by more than 60 investigators in the realms of MS, neuro ophthalmology, clinical trial design, and evaluation of clinical outcome measures from Europe, North America, Asia, and Australia.

First, the researchers examined optic neuritis associated with MS, which is common among patients. The symptoms are described as several days of visual loss and, often, peri orbital pain exacerbated by eye movements. Complete vision loss is uncommon, however. Improvement of vision takes place typically after about 1 month following symptom onset. About 95 percent of patients achieve 20/40 high contrast visual acuity (HCVA), although many patients experience decreases in vision related quality of life (QOL) after five to eight years. There are short term treatments, typically intravenous methylprednisolone, which can speed recovery, but nothing offers long term benefits. Optical coherence tomography (OCT) offers a good option, the researchers believe, in studying therapies for neuroprotection and repair in MS.

The attendees also believed that patient reported outcomes are equally, if not more, important than clinical outcomes in measures of visual function, structure, and electrophysiology in their relation to patient QOL.

“Ideally, visual measures used in MS clinical trials should be standardized, reliable, practical, tolerated by study participants, and applicable for both adult and pediatric populations,” the authors wrote. “Aspects include visual function, vision specific QOL, structural markers, and electrophysiological tools.”

More comprehensive studies of visual dysfunction as secondary outcomes in clinical trials are needed, and particularly for progressive MS, the attendees determined. But more trials which aim to improve visual outcomes following optic neuritis are needed, as well.

“It is imperative that trials focusing on acute optic neuritis have sufficiently stringent eligibility criteria to insure accurate diagnosis and to avoid enrolling participants with other forms of optic neuropathy or causes of visual loss,” the authors concluded. This is especially true in pediatric MS cases, although they are rare, which present many study challenges for researchers, the authors reported.

“The capacity for measures of visual function, QOL, visual pathway structure, and electrophysiology to show not only deterioration but also improvement will be critical in the emerging era of agents that repair and protect the nervous system,” the authors said. “Vision research in MS will continue to require and benefit from the collaborative approach that has contributed to its success over the past decade.”

Source: HCP Live © HCP Live 2015 (09/02/15)

Could anatabine citrate be a used as a multiple sclerosis therapy?(03/02/15)

Drug development company Rock Creek Pharmaceuticals has announced a new clinical trial application with the Medicines Healthcare Products Regulatory Agency (MHRA) has been approved. The company is set to proceed with a Phase I study of Anatabine Citrate, a chemical that is found naturally in aubergine, potatoes, green tomatoes and other members of the Solanaceae family of plants, as well as in tobacco and tobacco smoke. The chemical is known for its anti-inflammatory properties unique from other anti-inflammatory drugs on the market, and may benefit patients with multiple sclerosis (MS).

The Phase I study will evaluate Anatabine’s pharmacokinetic profile in the form of modified release formulation prototypes, and its safety and tolerability profiles in healthy volunteers. The first two parts will involve an open-label, non-controlled, single-dose study on 14 healthy participants, using six formula variations, with each administered dose spaced 7-14 days apart. The variations will be distinct in dose and duration of therapeutic action. This will allow the company to determine which formulation is most ideal, based on safety. The third and last part of the Phase I study will be a double-blind, placebo-controlled, seven-day multiple dose study of the identified optimal formulation in healthy subjects.

“We are delighted to have been granted regulatory approval to begin our Phase I studies in the UK. This is the first clinical phase for our lead drug and will focus on safety and tolerability of six different formulations, five of which have modified release profiles and are of different doses. We look forward to generating our first human clinical data under this CTA,” said Rock Creek Pharmaceuticals CEO Dr Michael Mullan.

Rock Creek’s UK-based partner, Quotient Clinical, is set to begin enrollment of healthy subjects this month. While the company expects the study to stretch well into August, they expect to have a significant amount of research findings by mid-2015. Rock Creek also announced Quotient Clinical will be utilizing its RapidFACT® (Rapid Formulation development And Clinical Testing) service to hasten the development of these novel, oral, modified release formulations that have been co-developed between the two companies.

Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (03/02/15)

Study looks at glucose and MS(03/02/15)

A study by researchers from Finland and Colorado have found that there may be a link between how the body deals with glucose and mobility in people with MS.

Eight patients with MS and eight controls performed 15 minutes of treadmill walking at a self-selected pace, during which the glucose analogue [18F]-Fluorodeoxyglucose (FDG) was injected. Immediately after the period of walking, the participants underwent a positron emission tomography (PET) scan.

Patients with MS had lower FDG uptake in 40 per cent of the brain compared to the healthy controls and walked at a slower speed. Within the area of lower FDG uptake 15 regions were identified. Of these, 13 were found to have strong to moderate correlations to walking speed within the healthy controls. Within patients with MS, only three of the 15 regions showed significant correlations.

The researchers concluded that walking impairments in patients with MS may be due to network-wide alterations in glucose metabolism. |It is hoped that understanding how brain activity and metabolism are altered in patients with MS will allow for better measures of disability and status of the condition.

Source: Frontiers © 2007 - 2015 Frontiers Media S.A. (03/02/15)

Phase I trial data for remyelinating antibody in MS released(02/02/15)

Acorda Therapeutics has today announced safety and tolerability data from a Phase 1 clinical trial of rHIgM22, a remyelinating antibody being studied for the treatment of multiple sclerosis. The trial, which followed participants for up to six months after receiving a single dose of rHIgM22, found no dose-limiting toxicities at any of the five dose levels studied. Based on this, the Company intends to advance clinical development of rHIgM22.

“We’re encouraged by the outcome of this trial, which showed that rHIgM22 was well-tolerated at all of the dose levels we studied,” said Anthony Caggiano, M.D., Ph.D., Acorda’s Senior Vice President of Research and Development. “We are currently developing the protocol for our next Phase 1 clinical trial of rHIgM22. The data from this study will help inform the design of the next trial, which will enroll people with MS who are experiencing an active relapse.”

This was a multi-center, double-blind, randomized, placebo-controlled study designed to evaluate safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of rHIgM22 in participants with any type of MS who were clinically stable for at least three months. All participants remained on their existing MS treatment regimens, including disease-modifying therapies.

The first part of the study included five cohorts, with each cohort receiving a higher dose of rHIgM22 than the previous one. Each cohort consisted of 10 participants (eight receiving drug, two receiving placebo), who were followed for three months after receiving a single dose of study medication. In the second part of the study, 21 participants were randomized to receive placebo or one of the two highest doses of rHIgM22 from the first part of the study. These participants were followed for six months to assess safety and tolerability. The second part of the study also included several exploratory clinical, imaging and biomarker measures, which are still being analysed. The study was not powered to determine statistical significance on these measures.

Additional details from the trial will be presented at future medical meetings.

Across all of the study groups, 55 participants received one of the five doses of rHIgM22 and 17 received placebo (no sample size power calculation was used to determine the number of participants in each group). There were no dose-limiting toxicities and no serious adverse events (SAE) in any of the five rHIgM22 dose levels in the study. There was one SAE of squamous cell carcinoma in a placebo-treated participant.

The most commonly observed adverse events (>5 per cent in the combined rHIgM22 treatment groups) reported in the study were: headache, contact dermatitis, MS relapse, infusion site hematoma, fatigue, arthralgia, back pain, muscular weakness, neck pain, pain in an extremity, pruritus, contusion, and flushing. No participants withdrew due to adverse events.

No safety signals were identified by standard clinical MRI evaluations, or standard clinical, laboratory or ECG assessments.

rHIgM22 is a recombinant human monoclonal antibody identified in the laboratory of Moses Rodriguez, M.D. at Mayo Clinic. In preclinical studies, rHIgM22 has been found to protect oligodendrocytes and stimulate them to repair areas of demyelination. rHIgM22 treatment also resulted in sustained improvements in motor activity in preclinical models.

Source: Finances © 2015 Finances International Ltd. (02/02/15)

Australia gets cutting-edge microscope(02/02/15)

The "secrets of life" could be revealed by a powerful new microscope, the only one of its kind in Australia.

THE $5million, three-metre tall microscope, unveiled at Monash University in Melbourne, allows researchers to see molecular structures at very high resolution.

"This is one of the most exciting days of my life," said Professor James Whisstock, the Australian Research Centre's director of advanced molecular imaging.

Professor Whisstock hopes the microscope will lead to better treatments for cancer, diabetes and multiple sclerosis.

"Understanding our immune system is central to fighting cancer, infectious diseases such as malaria, and auto-immune diseases such as diabetes, rheumatism and multiple sclerosis.

"The key to understanding and treating these diseases lies in understanding how proteins and cells interact at the molecular level."

Professor Whisstock said the instrument highlights how physics and engineering together can be used to answer biological problems.

"We need physicists and engineers to be able to build these devices that can see the secrets of life."

Until now Australian scientists had to travel to Europe, the UK or the US in order to access similar microscopes.

"The problem with that is transporting biological material internationally is quite hard."

The Dutch-made Titan Krios instrument works by firing electrons through a sample.

Some of the electrons in the beam are deflected and these rays can be used to create a 2D image of the sample. Multiple 2D images can then be automatically pieced together to create 3D images of molecules.

Source: The Australian (02/02/15)