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MS News Archive May 2015

Study shows MS patients are living longer (29/05/15)
People living with multiple sclerosis may be living longer than before, but when compared to those who do not have the condition their life expectancy is still shorter.

According to a new study, individuals with multiple sclerosis live nearly 7.5 years less when compared to those without the neurological condition.

"Despite studies that show MS survival may be improving over time, the more than 2.3 million people affected worldwide still face a risk of dying earlier," said Ruth Ann Marrie, co-author of the study and a member of the American Academy of Neurology (AAN).

For the purpose of the study, the researchers observed the death records and the billing data from the health system of 5,797 people with MS in a specific province in Canada from 1984 to 2011.

The research team also studied the health system records of 28,807 individuals who did not have MS and were of the same gender, stayed in the same region and were of the same age.

Those with the neurological disorder lived for an average of 76 years.

The researchers discovered 44 percent people who had MS passed away due to the condition and resulting complications.

The team also took note of other medical conditions such as epilepsy, diabetes or depression in the subjects, which possibly played a role in shortening their life expectancy. However, they discovered that alternate conditions only affected the life expectancy in people with multiple sclerosis just as they would for people without the condition.

That said, people with MS and other conditions such as diabetes, had a shorter life expectancy when compared to individuals with MS who did not have other issues.

The study was published in the AAN's medical journal Neurology.

Source: Tech Times Copyright 2015 (29/05/15)

Exercise improves outcomes in multiple sclerosis patients (29/05/15)
A continuous management program of prescribed exercise for patients with multiple sclerosis (MS) successfully reversed disease-related decline in the majority of patients, according to data presented at the Consortium of Multiple Sclerosis Centers 2015 Annual Meeting.

“MS patients are told this is a progressive disease and it is, but, clinically speaking, we've seen patients improve over long periods of time and continue to improve,” study presenter John Marmarou, DPT, MSCS, of Total Rehab & Fitness in Cherry Hill, NJ, told Neurology Advisor. “Patients were falling less, walking further and faster, and improving in cognition and hand function.”

Total Rehab & Fitness, a freestanding multidisciplinary practice, offers evidence-based rehabilitation services for patients with MS. The disease management program features a continuous model that addresses disabilities and impairments, while striving to improve and maintain lost function, enhance quality of life, and lower health care costs. It includes physical, occupational, hand, speech, cognitive, and behavioural therapy.

Marmarou and colleagues examined the efficacy of this program in 50 randomised patients (72 per cent women), who were included if they were in the program for at least 12 months (mean, 18 months) and had at least a 68 per cent attendance rate.

According to results, 92 per cent of patients demonstrated an improvement in MS functional composite score, with an average improvement of 15 per cent. In addition, researchers reported the following data:

72 per cent improved in 25-foot walk test time
96 per cent improved in 9-Hole Peg Test (HPT) time in the dominant hand
90 per cent improved in 9-HPT time in the non-dominant hand
90 per cent improved in Paced Auditory Serial Addition Test score
82 per cent improved in the 6-minute walk test distance
86 per cent improved in fall frequency

“Early intervention is key with [MS] patients,” Marmarou said.

“More people are being diagnosed with MS every day. We need to be thinking of … out-of-the-box ways to deliver care and not let third-party payers dictate care, which ultimately affects patients' quality of life. If there is a way to get patients the care they need regardless of their ability to pay, it improves their quality of life and saves community and federal government resources, as well as third-party payers.”

Going forward, Marmarou said he would like to see a larger, highly controlled study performed on the disease management program in hopes that this form of treatment can become the new standard of care. However, for now, “interpret the findings with caution,” he said.

Source: Neurology Advisor © 2015 Haymarket Media, Inc (29/05/15)

Researchers show neuroprotective effects of Lanthionine Ketimine Ester (26/05/15)
Exploratory research conducted at Virginia Commonwealth University and the University of Illinois at Chicago may translate into a new therapeutic agent to treat progressive multiple sclerosis, reports Multiple Sclerosis News Today.

Researchers in the laboratories of Dr Jefferey L. Dupree and Dr Douglas L. Feinstein tested a new compound in mice with induced multiple sclerosis and found the compound reduced neurodegeneration and helped improve symptoms.

The compound, lanthionine ketimine, is a naturally occurring molecule that binds to collapsin response mediator protein-2 (CRMP2), which is a protein found in the brain that helps regulate vital neuronal activities. In order to use this compound to treat mice with induced multiple sclerosis, the researchers needed to chemically modify it into a cell-permeable state. The resulting molecule was lanthionine ketimine ethyl-ester (LKE), which was shown to promote neurogenesis and healthy nervous system function.

As explained in the journal article, “Lanthionine Ketimine Ester Provides Benefit in a Mouse Model of Multiple Sclerosis,” which was published in Journal of Neurochemistry, the authors induced multiple sclerosis in mice using the well-accepted model of experimental autoimmune encephalomyelitis (EAE). After mice began to show moderate clinical symptoms of multiple sclerosis, the researchers mixed LKE into the animals’ food so that mice were treated whenever they decided to eat.

After four weeks of ingesting LKE, mice had lower levels of inflammation than those that did not receive LKE but were induced with EAE. LKE-treated mice also showed lower degeneration of the optic nerve and spinal cord, showing only minimal damage to the myelin sheath around the axons. The protective effect was more pronounced in the optic nerve, but the spinal cord also showed great benefit from LKE treatment.

If the researchers continue to pursue LKE and design a well-controlled dosing study in other animal models of multiple sclerosis, the compound may be a potential candidate for clinical trials in patients with progressive multiple sclerosis.

“Only few drugs have been shown to reduce neurodegeneration in multiple sclerosis,” stated the authors. By identifying neuronal protection in the spinal cord and optic nerve, the researchers showed that LKE is a novel and strong candidate for testing in progressive multiple sclerosis.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (26/05/15)

Brain implant senses 'intent' to move robotic arm (22/05/15)
A new kind of brain implant senses a patient's intent to move a robotic arm, offering new promise to people who are paralyzed or have lost limbs, researchers claim.

Erik Sorto, 34, is "the first person in the world to have a neural prosthetic device implanted in a region of the brain where intentions are made," said the study in the journal Science.

Sorto, who was paralysed from the neck down at age 21 after a gunshot wound, can now make a hand-shaking gesture, grab a cup to drink from and even play "rock, paper, scissors" with his robotic arm.

Previous attempts to use brain implants to control prosthetics have been placed in the motor cortex, which controls motion.

This experiment was done by placing two micro-electrode arrays in the posterior parietal cortex, or PPC. This part of the brain processes plans for movements including reach and grasp.

"When you move your arm, you really don't think about which muscles to activate and the details of the movement -- such as lift the arm, extend the arm, grasp the cup, close the hand around the cup, and so on," said principal investigator Richard Andersen, professor of neuroscience at Caltech.

"Instead, you think about the goal of the movement, for example, 'I want to pick up that cup of water.' So in this trial, we were successfully able to decode these actual intents, by asking the subject to simply imagine the movement as a whole, rather than breaking it down into a myriad of components."

The result is a more fluid movement than the jerky kind of motions seen in previous experiments, scientists said.

Sorto received the brain implant in 2013 and has been practicing with it at Rancho Los Amigos National Rehabilitation Centre ever since, learning to control a robotic arm that is not attached to his body.

He was able to control the arm in his very first attempt, about two weeks after his brain surgery.

Video images released by the science team show Sorto controlling a computer cursor, drinking a beverage and making a hand-shaking gesture with the arm.

"I was surprised at how easy it was," said Sorto, a single father of two.

"I joke around with the guys that I want to be able to drink my own beer - to be able to take a drink at my own pace, when I want to take a sip out of my beer and to not have to ask somebody to give it to me. I really miss that independence," he added.

"I think that if it were safe enough, I would really enjoy grooming myself - shaving, brushing my own teeth. That would be fantastic."

The clinical trial was a collaboration between Caltech, the Keck School of Medicine of the University of Southern California (USC) and Rancho Los Amigos National Rehabilitation Centre.

"These very important early clinical trials could provide hope for patients with all sorts of neurologic problems that involve paralysis such as stroke, brain injury, ALS and even multiple sclerosis," said co-author Christianne Heck, associate professor of neurology at USC.

Source: The Daily Mail © Associated Newspapers Ltd 2015 (22/05/15)

Treatment follow-up reveals positive results for MS patients (21/05/15)
Results from the BENEFIT11 trial has found that early treatment with IFNB-1b leads to improvements in cognition and fatigue in the long-term, as well as sustained employment and favourable magnetic resonance imaging (MRI) outcomes, measured at the 11-year mark, according to the study Long-Term Impact Of Early MS Treatment With Interferon Beta-1b: Clinical, MRI, Employment And Patient-Reported Outcomes (PROs) at the 11-Year Follow-up of BENEFIT (BENEFIT 11).

The BENEFIT trial included patients with MS and clinically isolated syndrome. Clinically isolated syndrome consists of an initial attack on myelin in the central nervous system, putting someone at risk for developing MS.

People who participated in the BENEFIT study either received IFNB-1b or a placebo (sugar pill). After the second case of clinically isolated syndrome, or after two years, all participants in the study were given IFNB-1b. The researchers measured MRI, performed laboratory tests, and took measurements about other outcomes eleven years after the beginning of the study.

278 MS patients participated in the study. At year 11, those who had received IFNB-1b still had a lower overall yearly relapse rate and a longer time to their first MS relapse than people who received placebo. They also had a lower incidence of clearly diagnosed MS. The expanded disability status scale (EDSS) score — a measurement of impairment used in people with MS — was the same in both groups. The paced auditory serial addition test (PASAT) scores, a measurement of cognitive ability, were high in both groups. Of the 81% who were employed when their physician first diagnosed their clinically isolated syndrome, 73 per cent were still employed.

A total of 12 per cent had retired early or were receiving long-term disability, as opposed to 2.9 per cent at the beginning of the study. Furthermore, 64 per cent did not take any sick leave for the most recent year. Health-related quality of life did not change. A total of 46 per cent of study subjects experienced no fatigue. Both groups had similar MRIs. A total of 86 per cent had no gadolinium-enhancing lesions, indicators of areas in which myelin is damaged.

In their report, the researchers concluded that “results from BENEFIT11 support a long-term impact of early treatment with IFNB-1b on clinical measures, including cognition and fatigue, and health economic and MRI outcomes.”

Source: Multiple Sclerosis News Today © BioNews Services 2015 (21/05/15)

Scientists identify cause of balance problems (20/05/15)
New research into the causes of the excessive inflammation that drives multiple sclerosis has identified a faulty "brake" within immune cells, a brake that should be controlling the inflammation. This points to a potential target for developing new therapies to treat MS and could have important implications for other autoimmune diseases, such as the colon disease colitis and the chronic skin condition atopic dermatitis, say researchers.

Further, the work has produced new research models of MS symptoms such as movement disorders and balance control problems that have, until now, resisted efforts to mimic them effectively in the lab. These models represent important new tools in the efforts to better understand - and eventually cure - MS and other autoimmune conditions.

The researchers determined that a mutation in the gene Nlrp12 was causing immune cells known as T cells to go haywire. Normally, the researchers determined, the protein the gene produces acts as a brake within T cells to control the inflammatory response. But a mutation in that gene disrupts the natural process and provokes severe inflammation - with effects the researchers found most intriguing.

To the researchers' surprise, the resulting inflammation did not produce the paralysis often associated with MS. It did, however, produce other MS symptoms - such as movement disorders and problems with balance control - which scientists have struggled to replicate in experimental lab settings.

"It's important to note that MS is a spectrum disorder - some patients present with paralysing conditions and some patients don't," said researcher John Lukens, PhD, of the University of Virginia School of Medicine Department of Neuroscience and its Center for Brain Immunology and Glia. "Not everybody's symptoms are the same, so this might give us a glimpse into the etiology or pathogenesis of that family of MS."

By blocking the inflammatory response, doctors may one day be able to control the symptoms it causes, both in MS and in other diseases driven by hyperinflammation.

The findings have been published by the scientific journal Immunity. Source: Science Newsline (20/05/15)

Discovery of a treatment to block MS progression (20/05/15)
A drug that could halt the progression of MS may soon be developed thanks to a discovery by a team at the CHUM Research Centre and the University of Montreal.

The researchers have identified a molecule called MCAM, and they have shown that blocking this molecule could delay the onset of the disease and significantly slow its progression. These encouraging results from in vitro tests in humans and in vivo tests in mice have been published in the Annals of Neurology. "We believe we have identified the first therapy that will impact the quality of life of people with MS by significantly reducing the disability and the disease's progression," said Dr. Alexandre Prat, lead author of the study, researcher at the CRCHUM, and professor in the Department of Neurosciences at the University of Montreal.

The brain is normally protected from attacks by the blood-brain barrier. The blood-brain barrier prevents immune cells - lymphocytes - from entering the central nervous system. In people with MS, there is often leakage. Two types of lymphocytes, CD4 and CD8, find a way to cross this protective barrier. They attack the brain by destroying the myelin sheath that protects neurons, resulting in decreased transmission of nerve impulses, and plaque formation.

In 2008, Dr. Prat's team identified a cell adhesion molecule, called MCAM (Melanoma Cell Adhesion Molecule), which plays a crucial role in dysregulation of the immune system observed in MS.

"Our studies have shown that MCAM is necessary for the migration of CD4 and CD8 across the blood-brain barrier. If we block the interaction of MCAM with the protein to which it normally binds, we decrease the disease's activity," he said.

Independently, the biotechnology company Prothena Corporation plc also discovered complementary data regarding MCAM, which led to an ongoing collaboration between the CRCHUM and Prothena.

"We observed a decrease of approximately 50 per cent of the condition in mice with experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. What is especially significant is that we can stop it from the first symptoms in addition to having an impact on its progression, which is a first," noted Prat.

MS develops in most patients in two phases. For 10 to 15 years, there are outbreaks of symptoms interspersed with remissions. Later, the diseases progresses and the disability worsens, leading to the use of a cane or wheelchair. Currently, none of the drugs available on the market affect progression.

Prothena has developed a potentially disease-modifying antibody, called PRX003, which is designed, to inhibit MCAM function and thus prevent migration of destructive lymphocytes into tissue. Prothena expects to initiate clinical trials of PRX003 in healthy volunteers by the end of June, and anticipates a study in patients with psoriasis in 2016. Beyond psoriasis, anti-MCAM antibodies may be useful for treating a variety of diseases, including progressive forms of multiple sclerosis.

Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (20/05/15)

Researchers solve MS ‘puzzle’ (18/05/15)
Evidence has long suggested multiple sclerosis is an autoimmune disease, but researchers have been puzzled because they found the same T cells that attack the myelin sheathing around nerve cells in MS patients are present in healthy subjects as well.

Now researchers from the Yale School of Medicine and colleagues at the Massachusetts Institute of Technology (MIT) report that auto-reactive T cells in MS patients produce different types of inflammatory hormones called cytokines than they do in healthy subjects.

“In most people, these T cells are acting to repair tissue, but in MS patients, they do damage to the nervous system,” said Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and senior author of the study, published May 14 in the journal Science Translational Medicine.

The Yale-led team analysed T cell populations from 23 MS patients and 22 healthy controls. Existing drugs target the MS-specific cytokines identified in the study and should be a promising new treatment for the disease, the authors say.

Hafler also noted the same sort of process might be found in other autoimmune diseases, such as rheumatoid arthritis and Type 1 diabetes.

Yonghao Cao of Yale and Brittany A. Goods of MIT are co-first authors of the paper.

The research was funded by the National Institutes of Health and the National Multiple Sclerosis Society.

Source: Bioscience Technology © Copyright 2015 Advantage Business Media (18/05/15)

Gene linked to interferon-beta treatment (18/05/15)
A new study led by investigators at Brigham and Womens Hospital (BWH) reports the discovery of a genetic variant associated with a patients likelihood of responding to interferon-beta, one of the medications used in treating multiple sclerosis.

Published in the Annals of Neurology, the study also presents evidence that the affected gene, SLC9A9, may have a broader role in regulating the development and activity of certain immune cells that play important roles in inflammatory diseases like MS.

The variant most predictive of whether or not a patient would respond to the drug was found in the gene SLC9A9.

"This study highlights the fact that genetic variation has a role in the course of a patient's MS, but that this role is modest and will require much larger studies to be understood in detail," said Philip De Jager, MD, PhD, who directs the Program in Translational NeuroPsychiatric Genomics at the Ann Romney Center for Neurologic Diseases at BWH.

A large, ongoing study of MS patients called CLIMB, based out of the Partners Multiple Sclerosis Center, was integral to the current work and will continue to follow patients over the course of treatment to identify predictors of future disease course and the effectiveness of treatments.

Additional support was provided by the National MS Society, Fondazione Italiana Sclerosi, the French MS society Association pour la recherche sur la sclerose en plaques, the Club francophone de la SEP, and the Reseau francais pour la genetique de la SEP.

De Jager is a recipient of the prestigious Harry Weaver Neuroscience Scholar of the National MS Society.

Source: Demanjo Copyright © Demanjo 2015 (18/05/15)

New insights into MS treatment (18/05/15)
Data from two Novartis phase III clinical trials show that adding brain shrinkage (brain volume loss) to an existing tool to assess multiple sclerosis activity (m-Rio) will give a more precise prediction of the likelihood of future disability progression.

A pooled analysis from the two-year Freedoms and Freedoms II trials also further confirm the high efficacy of Fingolimod in previously treated patients with highly-active relapsing MS. In the trials, patients on Fingolimod achieved no evidence of disease activity (Neda) across four key measures: relapses, MRI lesions, brain shrinkage and disability progression. Achieving Neda is especially critical for highly-active RMS patients, who are likely to lose more physical and cognitive functions over time despite being treated.

The Fingolimod clinical trial data was presented at the 67th American Academy of Neurology annual meeting in Washington, DC. Developed by Novartis, Fingolimod is the only oral disease-modifying therapy to impact the course of relapsing MS with high efficacy across four key measures of disease activity: relapses, MRI lesions, brain shrinkage (brain volume loss) and disability progression.

“Accurate assessment of disease activity is key to guide treatment decisions in relapsing MS. These data on Fingolimod and new methods of assessing the impact of MS have the potential to give physicians a more comprehensive picture of an individual’s disease and allow patients to better understand their MS,” said Dr Ludwig F. Damian, consultant neurologist.

“Novartis is committed to innovation beyond the research and development of new treatments to help physicians and patients improve how MS is managed,” said Dr Nikolaos Tripodis, Novartis Healthcare Philippines president and managing director.

Source: © Copyright 1997-2015 (18/05/15)

Gut bacteria could hold key (18/05/15)
Gut bacteria could hold the key to treating conditions including multiple sclerosis, Parkinson’s and mental illness, scientists have said.

The trillions of intestinal bacteria affect every aspect of our health and the way we behave, say researchers.

Professor Simon Carding, who runs the gut health programme at the Institute of Food Research, said: “The human gut is the inner tube of life.

"It is home to hundreds of trillions of microorganisms.

"They outnumber the cells that make up the body by more than 10-to-one, but far from doing us harm, they are working to keep us healthy.”

Researchers say eating a varied diet makes the microbes more diverse and improves health.

But the intake of healthy bacteria has declined as people eat more processed food such as pizzas, pies and cereals.

Professor Carding, of East Anglia University, said: “Such changes are increasingly being associated with a number of chronic diseases including those that affect the brain.”

But by studying patients’ intestines doctors may be able to create tailored treatments, he said.

Scientists are working on moving healthy bacteria from a donor to a sick patient.

Recent studies show those with potentially deadly C-diff bacteria can be cured by such transplants.

Professor Carding believes many other conditions may be “improved or even eliminated” by the same bacterial transfer.

A new book, The Diet Myth, claims fast food kills off microbes that help us stay slim.

Author Tim Spector, professor of genetic epidemiology at King’s College London, says this partly explains rising obesity levels.

Source: Daily Express Copyright ©2015 Northern and Shell Media Publications (18/05/15)

Genzyme and Ablynx form MS pact (18/05/15)
Sanofi group Genzyme and Belgian biotech Ablynx have formed a pact to investigate the latter’s nanobodies against a target that plays an important role in MS, in the hope of targeting the neurodegeneration linked with the condition.

Under the research deal, Genzyme has bought itself the right to perform in vitro and in vivo research with Ablynx’s Nanobodies in MS-relevant models in return for an undisclosed exclusivity fee. When these studies are complete, Genzyme has the option of negotiating a license agreement.

Ablynx has already generated “potent” Nanobodies against the Genzyme’s target of interest and confirmed their activity in preclinical models, the firm noted.

Commenting on the move, Johanne Kaplan, who heads up Neuroimmunology Research at Genzyme, said the project supports its research “that includes the exploration of novel therapeutic platforms to address unmet needs in multiple sclerosis”.

Further terms of the deal were not released.

Source: PharmaTimes Copyright PharmaTimes 2015 (18/05/15)

Genzyme and Ablynx form MS pact (18/05/15)
Sanofi group Genzyme and Belgian biotech Ablynx have formed a pact to investigate the latter’s nanobodies against a target that plays an important role in MS, in the hope of targeting the neurodegeneration linked with the condition.

Under the research deal, Genzyme has bought itself the right to perform in vitro and in vivo research with Ablynx’s Nanobodies in MS-relevant models in return for an undisclosed exclusivity fee. When these studies are complete, Genzyme has the option of negotiating a license agreement.

Ablynx has already generated “potent” Nanobodies against the Genzyme’s target of interest and confirmed their activity in preclinical models, the firm noted.

Commenting on the move, Johanne Kaplan, who heads up Neuroimmunology Research at Genzyme, said the project supports its research “that includes the exploration of novel therapeutic platforms to address unmet needs in multiple sclerosis”.

Further terms of the deal were not released.

Source: PharmaTimes Copyright PharmaTimes 2015 (18/05/15)

Scientists find way to deliver drugs straight into people’s brains (15/05/15)
A team of Canadian scientists has found a way to break the barrier of the human body that keeps the nervous and circulatory systems apart, and inject the drugs directly into the brain using “carrier” antibodies.

That system known as the blood-brain barrier (BBB) protects the human skull from any microbes or chemicals, thus keeping the brain clean.

But this barrier also filters good things, such as disease fighting drugs from entering the nervous system. It only allows a selected few types of molecules to cross including water, some gases and lipid soluble molecules.

Scientists from the Canadian National Research Council have been battling for years to find a way to trick it and get the drugs to where they are most needed - to the human brain.

Currently, researchers say they have found a way based on the so-called “single domain antibodies” (SDA). It includes using special molecular fragments that are capable of tricking the blood-brain barrier (BBB) and making it believe they should be let through to the brain. The antibodies are able to squeeze past the barrier not just because of their size (these are fragments that consist of one molecule) but also due to being familiar to some of the receptors along the blood-brain barrier.

The single domain antibodies are exploiting the same mechanism that allows nutrients into the brain, and are able to bind chemically to other molecules.

The scientists add that the method allows them to target multiple types of diseases by producing different carrier molecules.

The method is part of the NRC's Therapeutics Beyond Brain Barriers (TBBB) program, which has been developing special carrier molecules for the past six years.

"It really opens the possibilities to use many different types of therapeutics for different diseases that we couldn't really use before unless we inject them directly into the brain which is highly invasive,” Dr. Danica Stanimirovic, the project`s scientific head,said.

Scientists add that it could become a significant step towards slowing the spread of brain diseases like Alzheimer’s, multiple sclerosis and Parkinson’s.

The discovery follows years of scientific work. At the moment drugs are usually placed into the blood and there they find a way around the body.

Still, researchers say it will take over a decade to finalise clinical trials.

Source: RT © Autonomous Nonprofit Organization “TV-Novosti”, 2005–2015. (15/05/15)

Treatment at the first sign of illness improves MS: Study (15/05/15)
A long-term study following multiple sclerosis (MS) patients taking interferon beta-1b, suggests the earlier therapy is started, the greater the benefit.

The results of the BENEFIT 11 study were published last week in Neurology.

In MS, the immune system mistakenly sees myelin, the protective covering of nerve cells, as an enemy to be destroyed. When a person has an MS attack the nerves are damaged and can result in a whole slate of symptoms that depend on the location of the inflammation.

The symptoms can be mild or dramatic. They can range from numbness and tingling to paralysis, cognitive issues, bowel and bladder problems, and even blindness.

Starting Early Is Key
For this study, researchers examined people who had suffered from clinically isolated syndrome (CIS), which is a singular neurological event resulting in symptoms similar to those seen in MS.

While the patients may appear to have the disease, doctors cannot give a definite diagnosis until after a person has at least two attacks. Each attack must result in lesions, or patches of inflammation, in different spots on the brain or spinal cord. Patients who have CIS have yet to meet this requirement and not all of them will go on to be diagnosed with MS.

Many will, however, so CIS is seen as a possible precursor to MS. By including these patients in this study, researchers were trying to catch MS in its earliest stage to see if treating with interferon beta-1b before the disease had time to do damage could make a difference in long-term outcomes.

Over the Long Haul
The original study randomly assigned participants to receive either interferon beta-1b or a placebo. After either a second neurological event or two years, all patients were given interferon beta-1b.

Researchers followed 278 patients over an 11-year period and found that people with CIS who received interferon beta-1b had a lower relapse rate and a longer time from first episode to receiving a definite MS diagnosis.

Early in relapsing MS, the body has the ability to heal damaged myelin to near perfect condition. Because of this, symptoms a patient suffers during an attack may disappear after the episode is over. But scar tissue accumulates over time. This scar tissue does not transmit nerve impulses as effectively as the original myelin. As a result, symptoms can remain and disability can accumulate.

For that reason, beginning treatment early — and taking it as prescribed — is crucial.

There are currently 12 disease-modifying therapies (DMTs) approved by the Food and Drug Administration (FDA) to treat MS. Each of these medications comes with possible side effects and varying levels of effectiveness.

According to a consensus paper published by the Multiple Sclerosis Coalition, “Early successful control of disease activity — including the reduction of clinical and sub-clinical attacks and the delay of the progressive phase of the disease — appears to play a key role in preventing accumulation of disability, prolonging the ability of people with MS to remain active and engaged, and protecting quality of life.”

Interferon beta-1b came on the market in 1993 as the first FDA-approved DMT for MS. It has been sold under the brand name Betaseron since that time. In 2014, the drug got a makeover. This version of the drug, called Extavia, only has to be injected twice a month.

Source: HealthlineNews Copyright © 2005 - 2015 Healthline Networks, Inc (15/05/15)

Celiac disease linked to increased risk of nerve damage (13/05/15)
People with celiac disease may be at higher risk of neuropathy, according to a new study published in JAMA Neurology.

Celiac disease can affect everyone differently, meaning it can be tricky to diagnose. However, digestive symptoms - such as diarrhea, vomiting, abdominal bloating and pain and weight loss - are most common in children, while adults with the condition are more likely to experience fatigue, bone or joint pain, arthritis or other non-digestive symptoms.

It is estimated that around 1% of the US population - the equivalent to 1 in 133 Americans - have celiac disease, though it is thought around 83% of these individuals are undiagnosed or misdiagnosed with other illnesses.

The association between celiac disease and neuropathy, or nerve damage, is not new. According to the researchers of this latest study, including Dr. Jonas F. Ludvigsson of the Karolinska Institutet in Stockholm, Sweden, it was first identified almost 50 years ago.

Untreated celiac disease has also been linked to increased risk of nerve-related conditions, such as multiple sclerosis (MS).

For their study, Dr. Ludvigsson and colleagues set out to determine the absolute and relative risk of neuropathy among a nationwide population-based sample of patients with a confirmed diagnosis of celiac disease.

2.5-fold increased neuropathy risk for patients with celiac disease
The study included 28,232 individuals from Sweden whose celiac disease was confirmed with small-intestine biopsies, alongside 139,473 age- and sex-matched controls.

The researchers identified 198 (0.7%) participants with celiac disease who were later diagnosed with neuropathy, while neuropathy was later diagnosed in 359 (0.3%) of control participants.

The team calculated that overall, participants with celiac disease were around 2.5 times more likely to receive a later diagnosis of neuropathy than those without celiac disease.

The absolute risk of developing neuropathy was estimated to be 64 per 100,000 person-years among participants with celiac disease, while the absolute risk of neuropathy was estimated at 15 per 100,000 person-years among participants free of celiac disease.

Commenting on their findings, the researchers say:

"We found an increased risk of neuropathy in patients with celiac disease that persists after celiac disease diagnosis. Although absolute risks for neuropathy are low, celiac disease is a potentially treatable condition with a young age of onset."

The team adds that the study indicates patients with neuropathy should be screened for celiac disease.

In November 2014, Medical News Today reported on a study suggesting that some non-gluten wheat proteins may trigger celiac disease.

Published in the Journal of Proteome Research, the study revealed that non-gluten proteins including serpins and purinins triggered a greater immune reaction among patients with celiac disease and dermatitis herpetiformis - a rash associated with the disease - than among those without such conditions.

Source: MNT © 2004-2015 MediLexicon International Ltd (13/05/15)

Immune system genes may change with the seasons: study (13/05/15)
When the seasons change, your immune system response may also change, researchers report.

These findings might explain why conditions such as rheumatoid arthritis and heart disease are worse in the winter than in the summer, the new study finds.

The researchers from the University of Cambridge analysed genes from more than 16,000 people worldwide, including those from both the Northern and Southern hemispheres. They found that the activity of nearly one-quarter of the genes differed according to the time of the year. Some are more active in winter and some are more active in summer, the research revealed.

Seasons also affect our immune cells, and the composition of our blood and fat, according to the study.

Findings were published May 12 in the journal Nature Communications.

It's been known that there are seasonal variations in a number of conditions, including heart disease, autoimmune disorders such as type 1 diabetes, multiple sclerosis and mental illness, as well as in vitamin D metabolism. However, the researchers said this is the first study to show that seasonal changes may affect immune system function.

"In some ways, it's obvious -- it helps explain why so many diseases, from heart disease to mental illness, are much worse in the winter months -- but no one had appreciated the extent to which this actually occurred," said John Todd, professor and director of the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory at the University of Cambridge.

"The implications for how we treat disease like type 1 diabetes, and even how we plan our research studies, could be profound," he said in a university news release.

One gene that was more active in the summer and less active in the winter has been shown to suppress inflammation in mice. If the same is true in people, those in the Northern Hemisphere would have higher levels of inflammation in the winter.

Inflammation is a risk factor for a number of diseases, which means that those at high risk might be more likely to have more health problems during the winter. Drugs that target inflammation may offer a way of treating these diseases more effectively in the colder months, the researchers suggested.

They also found that certain genes associated with people's responses to vaccines were more active in winter. This means that some vaccination programs might be more effective during that season.

"Given that our immune systems appear to put us at greater risk of disease related to excessive inflammation in colder, darker months, and given the benefits we already understand from vitamin D, it is perhaps understandable that people want to head off for some 'winter sun' to improve their health and well-being," Todd said.

Exposure to sun triggers vitamin D production in the body.

Source: HealthDay Copyright © 2015 HealthDay (13/05/15)

Problem drinking in MS associated with anxiety and family history (12/05/15)
A new study has put forward the suggestion of a relationship between mood disorders, suicidal thoughts, substance abuse and problem drinking in people with MS.

Researchers Susan Quesnel and Anthony Feinstein of the Department of Psychiatry, University of Toronto and Sunnybrook and Women’s College Health Science Centre in Ontario, Canada, sought to find out more about problem drinking, depression and suicide in people with MS.

The pair studied drinking patterns in 140 multiple sclerosis patients. The researchers sought to determine whether study participants had a lifetime history of psychiatric diagnoses using a standard assessment called the Structured Clinical Interview for DSM-IV disorders (SCID-IV). The DSM-IV refers to the Diagnostic and Statistical Manual of Mental Disorders used by clinicians and psychiatrists to diagnose psychiatric illness.

The research revealed that one in every six MS patients drinks to excess over the course of their lifetime. Those people with a history of problem drinking also had a higher lifetime prevalence of anxiety, but not mood disorders such as depression. In addition, people with a drinking problem also were more likely to have had suicidal thoughts over the course of their lifespan, as well as other substance abuse problems and a family history of mental illness. The researchers found that all of these associations were statistically significant.

In their report, the researchers said: “Clinicians should be aware of the possibility of problem drinking in MS patients, and how this may complicate the course of their disease. Clues to problem drinking in MS patients are the presence of a positive family history of mental illness and prominent anxiety.”

The researchers said comprehensive care of MS should ideally include monitoring for other commonly associated problems, such as depression, suicidal thoughts, drinking problems and anxiety. Understanding risk factors for the occurrence of these problems in MS can help patients and their families alike.

Source: Multiple Sclerosis News Today © BioNews Services 2015 (12/05/15)

Blood test study findings revealed (12/05/15)
Amarantus BioScience Holdings says it has reported preliminary data from the blood-based version of its MSPrecise® diagnostic, the Company's proprietary multiple sclerosis (MS) diagnostic test.

MSPrecise, a next-generation DNA sequencing (NGS) assay, measures DNA mutations found in rearranged immunoglobulin genes in immune cells (B cells) to identify patients with relapsing-remitting multiple sclerosis (RRMS) at first clinical presentation.

Results from the most recent MSPrecise validation study using cerebrospinal fluid (CSF) samples for MS, reported in January 2015, demonstrated an 86 per cent sensitivity and 71 per cent specificity in correctly identifying early-stage RRMS in subjects being evaluated for a demyelinating disease undergoing the current diagnostic standard of care (clinical evaluation, magnetic resonance imaging and oligoclonal banding tests), as adjudicated by an expert panel of physicians. When combined with oligoclonal banding tests (OCB), sensitivity improved to 96 per cent and specificity improved to 83 per cent.

In the study, preliminary results indicate the MSPrecise blood assay exhibited an 81 per cent sensitivity and 89 per cent specificity for identifying early-stage RRMS in subjects being evaluated for a demyelinating disease undergoing the current diagnostic standard of care. These results have not yet been combined with OCB and will require replication prior to moving into a CLIA validation study.

"These early findings are encouraging, and provide a pathway to further define and refine the MSPrecise blood assay," said Colin Bier, Chief Development Officer of Amarantus Diagnostics.

"Of particular importance, in this initial blood study, is the promising and positive analytical performance. There is such a high rate of misdiagnosis of MS, especially upon first clinical presentation of this chronic and extremely debilitating disease, that a blood test would be of great benefit to patients and physicians. We are preparing MSPrecise CSF for a CLIA-enabling validation study and, in parallel, will actively continue research and development of the MSPrecise blood assay."

Source: Nasdaq GlobalNewswire © 2015 GlobeNewswire, Inc (12/05/15)

'We expected our daughter's MS but it still felt like a bombshell' (11/05/15)
Childhood multiple sclerosis often goes undetected but Lucy Wood's early diagnosis at the age of five has been crucial in reducing her disability over time.

A photograph of 11-year-old Lucy Wood taken last September shows her smiling in her new uniform, ready for her first day at secondary school. In another photo she is wearing the same smile but is hooked up to a hospital drip as she receives her monthly dose of Tysabri, the drug that controls her multiple sclerosis.

Diagnosed with MS at the age of five, Lucy is one of fewer than 10 per cent of patients who suffer their first symptoms in childhood: most of the 100,000 people with the disease in the UK develop it in their 20s and 30s. She was lucky, however, to receive an early diagnosis. New research from the University of Manchester has found that childhood MS often goes undetected, sometimes for years.

According to lead author Professor Susan Kirk, the delay is due to “low levels of awareness in the general public and doctors about the existence of childhood MS,” as well as there being only “a small group of paediatric neurologists with the necessary expertise to make the diagnosis.”

While some 125 children under 15 in the UK experience a first MS-like “attack” each year – commonly a problem with vision - only around 20 per cent subsequently develop paediatric MS.

Doctors do not know why an initial attack is followed by further attacks in some children but not in others.

Lucy, from Peterlee in county Durham, was three when she experienced a temporary loss of vision in her left eye. Doctors suspected a rare nervous system disease called ADEM (Acute Disseminated Encephalomyelitis), which can cause similar symptoms to MS and which was successfully treated with steroids. Further problems with Lucy’s vision, balance, coordination and speech followed, but her parents were still told MS was unlikely. This was even though Lucy’s father, Stuart, 46, had been diagnosed with MS aged 27 – and having a parent with MS increases the risk from 1 in 600 to 1 in 50.

“We were told MS was incredibly unusual at Lucy’s age, but to me it was like watching Stuart develop the disease all over again. We became convinced our daughter had it,” says Sharon, 45, Lucy’s mother. An MRI scan in August 2008 confirmed Lucy’s parents’ worst fears.

“We expected it but it still felt like a bombshell,” says Sharon. “Stuart blamed himself, believing he must have passed it on. In the end, Lucy’s positive attitude helped him accept it.” The couple’s other daughter, Katie, 17, shows no signs of MS.

Lucy experiences fatigue and sometimes needs to use a wheelchair. But Tysabri, prescribed four years ago to help dampen the immune system’s attack on myelin, has been “life changing”, says her mother.

Dr Cheryl Hemingway, a consultant paediatric neurologist at Great Ormond Street Hospital, runs one of the largest clinics in the country for children with MS and other rare myelin-attacking disorders. Early diagnosis is crucial, she says, for reducing the accumulation of disability over time and enabling children to “get on with their lives.”

Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (11/05/15)

Study suggests stress in childhood could be factor in MS (11/05/15)
Researchers in Denmark say children who have gone through a divorce could be at a slightly increased risk of developing multiple sclerosis.

The study, Stressful Life-Events In Childhood And The Risk Of Multiple Sclerosis: A Danish nationwide Cohort Study, looked at the cases of 2.9m Danes born between 1968 and 2011. A stressful life event (SFLE) was classed as divorce, parental death or the death of a sibling before the age of 18. MS cases in the cohort were identified in the Danish Multiple Sclerosis Registry. Associations of SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in log-linear Poisson regression models.

Researchers found people exposed to any SFLE in childhood were at 11 per cent elevated risk of MS, compared to the “non-exposed”. Stratification by subtype of SFLE showed parental death and death of a sibling were not associated with MS risk. However, those exposed to divorce were at 13 per cent increased risk of developing MS compared to the “non-exposed”.

Source: University Of Southern Denmark (11/05/15)

 Tysabri review launched in Europe (11/05/15)

In light of growing evidence, the European Medicines Agency (EMA) has been asked to launch a review of the multiple sclerosis drug Tysabri to assess whether advice on managing known risks for progressive multifocal leukoencephalopathy (PML) should be revised.

PML is a rare brain infection caused by the JC virus (JCV), which has symptoms that may resemble those of an MS attack and may be fatal or result in severe disability. In addition to the presence of anti-JCV antibodies, other risk factors for PML are treatment duration, especially beyond two years, and immunosuppressant use before receiving Tysabri. Patients with all of the above risk factors have a significantly higher risk for PML.

Tysabri was approved in the European Union in June 2006 as a single disease-modifying therapy in highly active relapsing remitting MS (RRMS). It's indicated for patients with high disease activity despite treatment with a β-interferon or glatiramer acetate and in those with rapidly evolving severe RRMS. Tysabri was first approved by the US Food and Drug Administration (FDA) in November 2004.

The review will involve evaluating the data on the risk for PML, with the aim of better defining the risk and identifying further measures to minimize it and will be carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), which will make a set of recommendations. The PRAC recommendations will then be forwarded to the Committee for Medicinal Products for Human Use.

The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable to all EU member states.

The EMA has recently been made aware of new information in three key related issues, a statement from the agency notes:

Risk estimates: Tysabri treatment decisions are based on an algorithm in which the estimated PML incidences are calculated in a static way by pooling data from all sources (clinical studies, registries, spontaneous reports). However, interim data from the STRATIFY 2 study for patients with positive anti-JCV antibody status with and without a history of immunosuppressive treatment suggested a higher risk for PML than currently described in the algorithm.

Diagnosis of PML before the development of clinical symptoms: New data seem to suggest that asymptomatic PML cases have a higher survival rate (95.6 per cent) than do symptomatic cases (77.1 per cent). Current recommendations are to perform MRI within 3 months before initiating treatment and then annually. Recent literature suggests that more frequent MRI testing may detect a greater proportion of asymptomatic cases.

Anti-JCV antibodies: It was thought that a negative serologic anti-JCV antibody test suggested a very low probability of PML (about 0.01 per cent), but evidence from the AFFIRM and STRATIFY 1 studies showed nearly 13 per cent of negative patients could become positive during follow-up.

Currently, it's recommended that these patients be retested every six months for antibodies, but a more sensitive second-generation enzyme-linked immunosorbent assay was recently developed. Whether this affects current recommendations for antibody testing needs to be assessed.

Tysabri is a monoclonal antibody, administered through intravenous injection, that is designed to recognize and attach to a protein on the surface of leucocytes. By blocking this protein, the drug prevents leukocytes from going from the blood to the brain, thereby reducing inflammation and nerve damage caused by MS.

Source: Medscape Multispeciality Copyright © 1994-2015 by WebMD LLC (11/05/15)

Researcher takes sharper look at MS (07/05/15)
A young researcher at Massachusetts General Hospital is exploring ways to diagnose and track multiple sclerosis more accurately with stronger and faster imaging technologies.

Using ultra high-resolution magnetic resonance imaging (MRI) at Massachusetts General Hospital, a physician-scientist in the MGH Multiple Sclerosis Clinic is pioneering revolutionary new ways to see the disease in the brains of human patients. Ultimately, this improved imaging may permit doctors to more accurately track the disease in patients with multiple sclerosis (MS) and find ways to provide faster, better treatment and earlier diagnosis.

“MRI has really revolutionised the way we assess MS,” says Eric C. Klawiter, MD, assistant neurologist in Mass General’s Department of Neurology, who is leading efforts to use new MRI technologies to help MS patients.

Dr. Klawiter is also working with a super-fast MRI scanner unique to Mass General to study connections in the living brain. Developed as part of the National Institutes of Health Human Connectome Project, it’s a remarkable tool for MS research. Currently, a pilot study comparing brain connectivity data from healthy subjects and people with MS is underway, Dr. Klawiter says. It could yield clues for treating cognitive problems, which affect roughly half of people with MS.

Additionally, Dr. Klawiter hopes to use the scanner to develop reliable markers for MS, such as one that helps identify when myelin is being stripped away. A similar marker for axon damage, which may correlate with disability, might be even more useful. Finding these markers can greatly accelerate drug development. In addition, these imaging breakthroughs could lead to earlier diagnosis, which could allow doctors to take preventive steps that will help patients before the disease begins to take its toll.

Source: Massachusetts General Hospital © 2015 Massachusetts General Hospital (07/05/15)

Placenta cell focus of potential new treatment (06/05/15)
A study, Human Placenta-Derived Cells (PDA-001) For The Treatment Of Adults With Multiple Sclerosis: A Randomised, Placebo-Controlled, Multiple-Dose Study, published in the journal Multiple Sclerosis and Related Disorders and led by researchers at Mount Sinai in New York and Celgene Cellular Therapeutics, has revealed an infusion based on cells derived from the placenta proved to be safe for patients with multiple sclerosis and a promising new treatment for the condition.

It has been previously shown that therapeutic cell-based infusions have an immunomodulatory and repair action in MS. PDA-001 in particular is a preparation of cultured mesenchymal-like cells derived from healthy human placental tissue and designed for the treatment of MS as these cells have immunomodulatory, anti-inflammatory, pro-regenerative and neuroprotective properties. As these placenta cells are expanded in cell culture, one healthy donor is capable of supplying enough cells for several patients.

In the study, researchers tested the safety and possible exacerbation of the disease with this new MS treatment approach based on PDA-001. A phase 1b, randomised, multi-centre, double-blind, placebo-controlled study was conducted with 16 MS patients (ten with relapsing-remitting MS and six with secondary progressive MS), aged between 18 and 65 years. Six patients received a high dose of PDA-001 (600×106 cells), other six were given a lower dose (150×106 cells), and the remaining four patients received a placebo. Patients were monitored monthly for brain lesions.

Researchers found none of the patients had worsening of MS-related brain lesions one year after treatment with both PDA-001 doses, and the majority of the patients had stable or had improved levels of disability.

“We’re hoping to learn more about how placental stromal cells contribute to myelin repair,” said the study’s lead author and Professor of Neurology at Mount Sinai, Dr Fred Lublin in a news release.

“We suspect they either convert to a myelin making cell, or they enhance the environment of the area where the damage is to allow for natural repair. Our long-term goal is to develop strategies to facilitate repair of the damaged nervous system.”

The research team concluded that PDA-001 treatment was overall safe and well tolerated by patients, and that preliminary evidence suggests that PDA-001 could be able to repair damaged nerve tissues in MS patients.

“This is the first time placenta-derived cells have been tested as a possible therapy for multiple sclerosis,” said Dr Lublin.

“The next step will be to study larger numbers of MS patients to assess efficacy of the cells, but we could be looking at a new frontier in treatment for the disease.”

Source: Multiple Sclerosis News Today © BioNews Services 2015 (06/05/15)

Drug derived from sea anemone shows promise (06/05/14)
A drug developed from the toxin of a sea anemone to treat conditions such as multiple sclerosis have shown promise in a phase 1 clinical trial, it has been reported.

The drug, dalazatide, is being developed by Kineta Inc, and works differently from drugs currently used to treat immune disorders. They suppress the entire immune system, which puts patients at risk for infections, while dalazatide blocks only the white blood cells that trigger many autoimmune diseases.

"The results of this trial indicate an important advance in developing next-generation treatments for autoimmune disease that specifically regulate the immune response without broad immune suppression," Dr. Shawn Iadonato, Kineta’s chief scientific officer, told the Wall Street Journal.

Phase 1 trials are designed to test a drug's safety and tolerability using various dosages. Tested on patients with psoriasis, the group were given either 30 mg or 60 milligrams of dalazatide or a placebo by injections twice a week for four weeks.

Even though phase 1 trials are designed to test a drug's safety and tolerability, patients who received dalazatide, especially those getting the higher dosage, showed improvements in their psoriasis that continued during the month after the drug was stopped. In contrast, those patients taking a placebo experienced no changes.

Kineta hopes to begin recruiting patients next year for a phase 2 trial which will specifically test the drug's effectiveness.

The development of dalazatide is part of an ongoing effort to create medicines, including painkillers, from nature. Researchers have found, for example, that certain kinds of spider venom block the pathway that sends signals of pain from the nerves to the brain in a way that is non-addictive.

Source: Newsmax Health © 2015 NewsmaxHealth (06/05/14)

Patients with MS who smoke cannabis are more cognitively impaired than nonusers (06/05/14)
Effects of cannabis on cognition in patients with MS: A psychometric and MRI study.


OBJECTIVE: To determine functional and structural neuroimaging correlates of cognitive dysfunction associated with cannabis use in multiple sclerosis (MS).

METHODS: In a cross-sectional study, 20 subjects with MS who smoked cannabis and 19 noncannabis users with MS, matched on demographic and neurologic variables, underwent fMRI while completing a test of working memory, the N-Back. Resting-state fMRI and structural MRI data (lesion and normal-appearing brain tissue volumes, diffusion tensor imaging metrics) were also collected. Neuropsychological data pertaining to verbal (Selective Reminding Test Revised) and visual (10/36 Spatial Recall Test) memory, information processing speed (Paced Auditory Serial Addition Test [2- and 3-second versions] and Symbol Digit Modalities Test), and attention (Word List Generation) were obtained.

RESULTS: The cannabis group performed more poorly on the more demanding of the Paced Auditory Serial Addition Test tasks (i.e., 2-second version) (p < 0.02) and the 10/36 Spatial Recall Test (p < 0.03). Cannabis users had more diffuse cerebral activation across all N-Back trials and made more errors on the 2-Back task (p < 0.006), during which they displayed increased activation relative to nonusers in parietal (p < 0.007) and anterior cingulate (p < 0.001) regions implicated in working memory. No group differences in resting-state networks or structural MRI variables were found.

CONCLUSIONS: Patients with MS who smoke cannabis are more cognitively impaired than nonusers. Cannabis further compromises cerebral compensatory mechanisms, already faulty in MS. These imaging data boost the construct validity of the neuropsychological findings and act as a cautionary note to cannabis users and prescribers.

Pavisian B1, Macintosh BJ, Szilagyi G, Staines RW, O'Connor P, Feinstein A.

Sources: Neurology. 2014 Apr 30. [Epub ahead of print] & Pubmed PMID: 24789863 (06/05/14)

‘Personalised’ treatment results due next year (05/05/15)
After the Phase 2b clinical trial achieved full enrolment with 190 secondary progressive multiple sclerosis (SPMS) patients, Texas-based Opexa Therapeutics is now awaiting results for the company’s lead candidate, Tcelna, which are expected in the second half of 2016.

The therapy, which was spun off from a technology developed at Baylor College of Medicine (BCM) Technologies that was licensed and developed by Opexa, has shown efficacy in both SPMS and relapsing-remitting multiple sclerosis (RRMS) patients in earlier clinical trials.

“We have spent a good decade in clinical trials treating early- and late-stage multiple sclerosis,” said Neil Warma, President and CEO of Opexa Therapeutics, in an exclusive interview with Multiple Sclerosis News Today.

“In true fashion, we are trying to restore function of the immune system via personalized therapies that fight the root cause of disease itself.”

The focus of Tcelna is the interaction between T-cells and the rest of the body.

“It is similar in concept to a T-cell vaccine, but these ‘vaccines’ are personalized for patients with multiple sclerosis,” explained Warma.

“In patients with multiple sclerosis, there is a small population of myelin reactive T-cells (MRTCs) that cross into the central nervous system and attack nerve fibres. We isolate and identify those pathogenic T-cells, attenuate them, and reintroduce them back into the individual.”

First, a sample of blood is taken from a patient and sent to Opexa’s Good Manufacturing Practices (GMP) facility in Houston. Scientists then identify the specific myelin peptide antigens that the patient’s MRTCs recognize.

Out of 109 peptides screened by Opexa, typically three or four peptides are dominant, and are introduced to a population of expanding T-cells. After a few more manufacturing steps to attenuate the reactive T-cells, these are then shipped to the patient’s physician’s office, who receives a subcutaneous injection of the “T-cell vaccine.”

“The injection primes the body to selectively recognize and attack the MRTCs,” said Warma.

“It’s telling the immune system that these attenuated cells should be treated as foreign attackers.”

Although the injection delivers a bolus of MRTCs, the cells are attenuated, meaning they pose no risk of further destroying myelin. Instead, the cells die off and remain in situ long enough for the patient’s immune system to recognize the cells as damaging and harmful. With a heightened immune system, the patient’s own healthy T-regulatory cells search for MRTCs to remove them from the body in a sort of “anti-T-cell T-cell response.”

Traditional therapies wipe out the entire immune system and target all T-cells and other immune cells for destruction. Tcelna targets a select population of MRTCs, giving the treatment a better side effect profile and greater patient tolerability.

“Pharma looks at ‘personalised’ differently,” said Warma.

“They have a drug candidate that is effective in 10-20 per cent of patients, and they segment the market to serve those patients. At Opexa, we look at all multiple sclerosis patients and find a personalized therapy for every individual.”

Personalisation of treatment continues past the first dose. The optimal dosing schedule was found to be five subcutaneous injections each year, given in the first six months. An injection is given at one, two, three, four, and six months. In the next year, the injection pattern is identical, but patients receive a different formulation of T-cells.

“Each of our preparations is tailored specifically to match each individual’s profile. Each patient receives a specialized therapy,” Warma told Multiple Sclerosis News Today.

“Myelin peptide antigens change over time and are different for every individual. In year two, three, and beyond, we conduct the antigen screening process because we know these myelin peptides shift over time. We deliver a specific T-cell vaccine to each individual, relevant at that time.”

Source: Multiple Sclerosis News Today © BioNews Services 2015 (05/05/15)

Guanabenz studies underway (05/05/15)
The Myelin Repair Foundation (MRF), in partnership with the National Institutes of Health (NIH) has announced patients are now being enrolled in a clinical trial to study guanabenz, an FDA-approved drug to treat high blood pressure that was identified by MRF-funded researchers as a potential therapy to reduce loss of myelin in multiple sclerosis patients.

If successful, guanabenz (formerly called MRF-008) could be the first MS treatment to focus on protecting myelin from damage, which is the hallmark of MS, rather than on suppressing the immune system - as all currently available MS treatments do.

The trial, a collaboration between the MRF and the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) Clinical Centre, is being led by NIH Investigators Dr. Irene Cortese, M.D., and Dr. Daniel Reich, M.D., Ph.D.

Myelin is the membrane that surrounds and protects nerve fibres (axons) in the central nervous system.

In MS patients, the immune system damages myelin and the cells that produce and maintain it (oligodendrocytes). As the disease progresses, severe myelin degeneration is accompanied by axonal loss and neurodegeneration, all of which can profoundly disrupt signalling in the central nervous system and so leading to the array of symptoms that characterises MS.

Because loss of myelin correlates with neurodegeneration, new therapies that are designed to protect myelin or promote remyelination would be categorized as neuroprotective.

In a Nature Communications paper published in March, MRF-funded researchers reported that guanabenz prevents myelin loss and alleviates clinical symptoms of MS in animal models by prolonging an innate mechanism that is activated in response to stressors such as inflammation.

When this protective response is disrupted or overloaded - by the chronic inflammation seen in MS, for example - oligodendrocyte cell death and demyelination are significantly enhanced. Treatment with guanabenz strengthens this stress-response mechanism and helps protect oligodendrocytes from cell death. These findings point to promising avenues for the development of new treatments for MS.

"Guanabenz appears to enhance the cell's own protective machinery to diminish the loss of myelin," said senior study author Brian Popko, Ph.D., Jack Miller Professor of Neurological Disorders at the University of Chicago and a member of the Myelin Repair Foundation's Research Consortium.

"While there have been many efforts to stimulate remyelination, 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."

The MRF has supported Dr. Popko's research on the effects of inflammation on oligodendrocyte health and myelin production for more than ten years. In addition to Dr. Popko's team at the University of Chicago, MRF-funded researchers at Northwestern University in Chicago, Case-Western Reserve University in Cleveland, and scientists at the MRF's Translational Medicine Center in Sunnyvale, CA, made key contributions to the guanabenz publication.

The MRF's clinical advisory board reviewed the preclinical data and encouraged the MRF to advance guanabenz into clinical testing. The drug's protective efficacy and ability to alleviate myelin loss, coupled with its existing FDA approval and good safety profile, makes the clinical implications promising for MS patients, the advisory board concluded. However, before clinical studies could be initiated, the MRF had to identify a contract drug manufacturer to make clinical-grade guanabenz.

Because guanabenz has been off the market for many years, it is no longer manufactured anywhere in the world.

"We are very pleased guanabenz is now moving into studies in MS patients," said Tassie Collins, Ph.D., Vice President of Translational Medicine at the Myelin Repair Foundation.

"This is a promising approach, but it might not have been able to move forward without MRF's participation."

Because it is a generic drug, guanabenz would be an unlikely investment choice for pharmaceutical companies. And because it had to be custom-manufactured for the trial, most academic organizations would have been unable to resource it.

Source: Drug Research Drug Discovery & Development © PBR 2015 (05/05/15)