FDA approves electronic autoinjector for MS therapy (28/09/15)
The first electronic automatic injector to deliver a drug for the most common form of multiple sclerosis has received approval from the America’s Food and Drug Administration.
The injection delivers Betaseron, a disease-modifying drug approved 22 years ago by the FDA for relapsing forms of the incurable, often disabling disease of the central nervous system.
The new device, called Betaconnect, will be available in early 2016, said Bayer AG, which developed the injector and sells the drug.
The original device, through which Betaseron is delivered, was mechanically activated and makes a discernible sound during administration, which tends to disconcert patients, according to Amy Ross, former president of the International Organization of MS Nurses in America.
This new autoinjector, already available in Europe, reminds patients to take their medicine every other day, and is silent when used. It is customizable, allowing for adjustments in speed and depth of the injection, and has automatic needle retraction.
Although a sizable share of the MS market in the United States has been captured by oral drugs, including Biogen Tecfidera, reports linking some treatments to serious brain infections have tempered enthusiasm.
Doctors are now starting patients on injectable therapies - with an eye on long-term safety and efficacy - because many of these patients are quite young, said Ross, estimating about 50 per cent to 60 per cent of patients today are diagnosed in their 20s and 30s.
Source: Medical Daily © 2015 Medical Daily (28/09/15)
Study finds new drug reduces progression for primary progressive MS patients (28/09/15)
Genentech, a member of the Roche Group, has announced positive results from a pivotal Phase III study that evaluated ocrelizumab in people with primary progressive multiple sclerosis (PPMS). The study (ORATORIO) met its primary endpoint, showing treatment with ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo, as measured by the Expanded Disability Status Scale (EDSS).
Overall, the incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to placebo.
“People with the primary progressive form of MS typically experience symptoms that continuously worsen after the onset of their disease, and there are no approved treatments for this condition," said Sandra Horning, M.D., chief medical officer and head of Global Product Development.
“Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS.”
The positive study results observed with ocrelizumab in both people with PPMS (ORATORIO) as well as those with relapsing forms of MS (in the studies OPERA I and OPERA II) validate the hypothesis that B cells are central to the underlying biology of the condition.
Genentech plans to pursue marketing authorization for ocrelizumab in relapsing MS and in PPMS. Data from the OPERA I and II studies and from the ORATORIO study will be submitted to the U.S. Food and Drug Administration in early 2016.
Source: Business Wire © 2015 Business Wire (28/09/15)
Researchers reveal treatment for rare brain disease (25/09/15)
The discovery that specific antibodies play a key role in combating the viral infection progressive multifocal leukoencephalopathy (PML), a vaccine against the disease could now be developed, say researchers.
Humans carry a multitude of viruses and bacteria in their gut, on their skin and in other organs. Often, these are involved in important bodily functions. Under certain conditions, however, some can also cause diseases. The JC virus, a member of the polyoma tumor virus family, is a prime example. This pathogen was first isolated from the brain of a patient who was suffering from PML. The virus, which more than 60 percent of the global population are infected with, normally resides in the kidneys and certain other organs. JC virus can trigger the PML infection in the brain, which, in most cases, is fatal.
Two studies conducted by an international team of researchers from the University of Zurich, the University Hospital Zurich, the National Institutes of Health in the USA, San Raffaele Hospital in Milan, the University of Tübingen, and the UZH spin-off Neurimmune now reveal that the antibodies in PML patients often fail to recognize the JC virus they are infected with.
"In healthy people, the disease never breaks out as the immune system keeps it well under control. Once the immune system is compromised, however, such as in patients with tumors, leukemia, AIDS, autoimmune diseases and certain immunosuppressive treatments, the JC virus is able to alter its genetic information and infect the brain," explains Roland Martin, professor of neurology at the University of Zurich.
In MS patients, the treatment with a particular antibody, Tysabri, prevents immune cells from reaching the brain - but at the same time, also inhibits the brain's immunosurveillance. If JC viruses enter the brain during the treatment, they go undetected, which can cause PML. Over 560 MS patients worldwide have already developed the PML brain infection.
By vaccinating mice and a PML patient with the virus' coating protein, the international groups were able to demonstrate that the antibody response was so strong that the patient was soon able to eliminate the JC virus. The so-called active vaccination method was developed at the University of Zurich and the University Hospital Zurich, and has already been used successfully on two more patients. The JC-virus-specific antibodies that are of interest for the treatment of the existing brain infection were developed by the group at the University of Zurich and the University Hospital Zurich together with colleagues from the University of Tübingen and the biotechnology company Neurimmune in Schlieren.
"We made a major breakthrough," says Martin. "We managed to isolate antibody-producing cells from a patient who survived PML and use them to produce neutralizing antibodies against the JC virus. These human antibodies have a major advantage: they recognize the most important mutants of the JC virus that can cause PML. They now make promising candidates for the development of a treatment for PML."
Source: Advantage Business Media © Copyright 2015 Advantage Business Media (25/09/15)
Progression confirmation period too short to define disability persistence in MS (24/09/15)
Researchers recommend extending the minimum timeframe for confirming disability progression in multiple sclerosis (MS) from three–six months to 12 or 24 months to better distinguish true irreversible disability from relapse-associated transient disability.
The recommendation is based on their finding that a three-six month confirmation period overestimated the accumulation of permanent disability by up to 30 per cent, compared with up to 20 per cent and 11 per cent if a 12-or 24-month period is used, respectively.
“This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapse-remitting disease,” says the team.
Led by Tomas Kalincik (Royal Melbourne Hospital, Australia), the researchers used the global MSBase registry to evaluate 48 criteria for disability progression in 16,636 patients with MS who had a minimum of three Expanded Disability Status Scale (EDSS) scores recorded.
The median time between EDSS visits was 6.6 months and the cumulative captured follow-up was 112,584 patient–years, with a median follow-up per patient of 5.7 years.
Progression rates varied between 0.41 and 1.14 events per patient-decade with only 17.3 per cent of progression events identified by all 48 criteria simultaneously.
Over the subsequent 5 years, disability regressed in 11 per cent to 34 per cent of the progression events. The length of the disability confirmation period was the most important determinant, with the proportion of events regressing within five years decreasing with longer confirmation time, from 30 per cent at three months to 26 per cent at six months, 20 per cent at 12 months and 11 per cent at 24 months.
Indeed, a 12- or 24-month confirmed progression of disability combined with a baseline EDSS recorded at a single timepoint provided the most stable criteria for detecting disability progression and persistence at five years, correctly identifying 80–81% and 88–89% of persistent progression events, respectively. The two-strata and three-strata EDSS criteria for determining the magnitude of progression were comparable for identifying persistent progression events.
The researchers note in Brain that progression events confirmed for 3 months were the least persistent, with 22–26 per cent of such events regressing over the initial 10 years after progression, compared with just eight-nine per cent of those confirmed over a 24-month period.
Other factors increasing the likelihood of a progressive disability event were male gender, older age, progressive MS and a lower EDSS score, while regression of disability was more likely to occur among women, younger individuals and those with a relapse–remitting disease course.
Given their findings, Kalincik and colleagues recommend “implementation of longer disability confirmation period in the design of observational studies but also of prospective clinical trials.”
They add: “This is not impractical as most modern trials include open-label extension studies, and these observations can be used to define 12- and 24-month confirmations of disability progression events which occurred during the randomised stages of these trials.”
Source: News-Medical.Net Copyright 2000-2015 AZoM.com Limited (24/09/15)
Inhibiting LINGO-1 protein is potential treatment for cognitive impairment (24/09/15)
In a new study entitled “LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice”, scientists report that the loss of myelin in MS patients’ brains contributes to their cognitive impairment. They showed that inhibiting protein LINGO-1 can improve these cognitive deficits by promoting myelin growth, thereby establishing impairment of LINGO-1 as a potential new therapeutic avenue for cognitive deficits in MS patients.
The study was published in the journal Science Reports.
The researchers used mouse models for human MS, specifically the experimental autoimmune encephalomyelitis (EAE) mouse model, to investigate the link between myelin impairment and cognitive decline. Moreover, despite the high incidence of cognitive impairment in MS patients, the treatments available have no benefits in improving patients’ cognitive features. Hence, there is an unmet need for an effective treatment.
In the study, researchers observed that the deficits in both memory and learning skills occur at later stages of the disease. They followed previous studies suggesting that a protein called LINGO-1 (short for LRR and Ig domain containing NOGO receptor interacting protein 1) inhibits myelin production. Accordingly, the team used an antibody against LINGO-1 and discovered it significantly improved learning and memory in the EAE mouse model, while it activated the AKT/mTOR signaling pathway, a crucial regulator of myelin growth. This phenotype was accompanied by an increase and restoration of myelin basic protein (MBP) expression in the brain of these mice, a key protein in the myelination process of nerves.
These findings therefore suggest that demyelination may contribute to the learning and memory deficits of MS patients, and establish the potential action of LINGO-1 antibody as a strategy to promote myelin growth. Hence, inhibiting LINGO-1 protein is a potential future treatment for cognitive impairment in MS patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (24/09/15)
Review explores factors that influence quality of life in MS patients (22/09/15)
In a review published in the European Journal of Neurology, A. P. Lysandropoulos from the University of Brussels and E. Havrdova, from the University of Prague described some ‘hidden’ issues that influence the quality of life (QoL) in patients with MS.
In the review, researchers discussed the limitations concerning the measurement of QoL and provide early evidence for the benefits of specific psychological support on patients’ QoL.
QoL in patients with MS is influenced by factors beyond pathophysiology and disease progression, and is frequently at odds with objective measures of condition. MS patients may be well treated and free of symptoms but still have poor QoL due to patient-centred factors such as depression, inability to work and relationship issues.
In the review, “Hidden factors influencing quality of life in patients with multiple sclerosis”, the researchers firstly mentioned that amongst the first critical parameters influencing QoL in MS patients is the MS ‘label’. The mere thought of MS can strike fear in people even in the absence of any knowledge about the disease. At the time of an MS diagnosis, many patients immediately visualise themselves in a wheelchair, and this pessimistic perception of the condition determines the way in which a patient analyses his or her symptoms by amplifying them.
Cognitive impairment is another factor that is increasingly being recognised as part of life with MS, existing alongside physical symptoms and limitations. Since patients become less effective professionally and socially, impaired cognition can lead to a vicious cycle of frustration with negative impact on QoL. Cognitive issues can develop early in the course of MS, particularly with respect to processing speed and handling of complex information.
Sexual dysfunction is also frequent in MS patients, and it is reported to occur in up to three-quarters of women and up to 90% of men. Sexual dysfunction has been shown to have a greater detrimental effect on mental health aspects of health-related QoL in MS patients than the severity of physical disability.
Regarding MS as a family problem, a diagnosis of MS is traumatic not only for the patient but also for the patient’s family. Most MS patients are diagnosed at a relatively young age and it is only natural for parents to be concerned about their child. Life plans such as work, relationships and family planning may be adversely affected by MS, and feelings of anger, denial and fear are not limited to the patient but are also experienced by the family.
A real limitation regarding the measurement of QoL in MS patients is the lack of validated instruments. Traditional approaches used to measure QoL in MS tend to lack sensitivity to change, and the current repertoire of tools does not allow for easy assessment of all aspects of the disease, including the many hidden issues that influence QoL.
Physical and cognitive difficulties have a negative psychological impact on MS patients and, in turn, on their QoL. Psychological interventions for MS are necessary to address all the factors that influence QoL in patients. The beneficial effects of psychological support in MS patients may go beyond improved patient-centered outcomes and impact directly on disease activity.
The authors believe that, as with other chronic diseases, it can be argued that QoL is a more relevant outcome in MS patients than traditional measurements such as disability or neurological impairment. However, much work needs to be done before QoL assumes its rightful position as the primary outcome measure in clinical trials and clinical practice. According to the authors, elements that influence QoL in MS patients need to be better defined and there is a need to be clarified which of the many QoL instruments should be used and for what purposes. Moreover, the authors mentioned that more evidence is required of the benefits of psychological support strategies on both disease progression and QoL in MS patients.
The authors concluded that future studies are expected to better define the most suitable means of assessing patient-centered outcomes in MS, and identify the most appropriate management strategies for individual patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (22/09/15)
Gilenya found to be effective ‘for up to three years’ (22/09/15)
An encouraging new analysis reveals Gilenya is an effective MS therapy for a treatment period of up to three years. The results were presented at the Annual Meeting of the Consortium of MS Centres in America.
Gilenya, produced by Novartis, is an immunomodulatory drug able to reduce the rate of relapse in relapsing-remitting MS (RRMS) patients.
In the study, the team analysed data from three previously published phase 3 clinical trials (FREEDOMS, FREEDOMS II and TRANSFORMS) that assessed the use of Gilenya in RRMS patients compared to beta interferon or a placebo. The team found Gilenya 0.5 mg offered consistent clinical benefits to RRMS patients in comparison to placebo or beta interferon, irrespective of when the patient had the first symptom of the condition or the number of years of previous treatment.
The team reported that overall, Gilenya was able to significantly reduce the annualised relapse rate in patients with zero, less than three, and more than three years of therapy in comparison to placebo and beta interferon.
“We weren’t able to find any larger subgroup of patients who didn’t respond well,” said Dr. Daniel Ontaneda, assistant professor of medicine and neurology at the Cleveland Clinic, who presented the data.
“One might have had an intuition that patients over age 40, say, weren’t going to respond. But the clinical take-away is that the medication works equally well for almost everyone.”
The efficacy of Gilenya represents good news for the MS population, however, neurologists still have the difficult task of determining which of the currently available MS medications should be prescribed to a particular patient.
“We now have 12 available medications for MS,” noted Dr. Ontaneda. “For clinicians, the decision on which medication to prescribe is becoming ever more complex. We need to figure out if there are advantages for one type of patient versus another. Trying to identify responders and non-responders is something we need to continue to pursue.”
According to Dr. Timothy L. Vollmer from the University of Colorado School of Medicine, who was not involved in the study, the findings go against the position taken by a report from the Agency for Health Care Research and Quality (AHRQ). “The AHRQ consensus document said there is no evidence of drug benefit beyond two years,” said Dr. Vollmer.
“This study will push back against some of those insurer groups and the AHRQ. It’s consistent with what we’ve all been saying, that we don’t see any loss of efficacy in patients kept on Gilenya for a long time.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (22/09/15)
Benefits assessments affecting claimants health (14/09/15)
People living with multiple sclerosis who are required to undergo assessments to claim disability benefits are having their health damaged as a result, reports The Guardian.
The MS Society found that nearly half (48 per cent) of people with the disease of the nervous system who had an assessment for Employment Support Allowance (ESA) felt the process caused their condition to deteriorate or relapse. Just over a third who had a face-to-face assessment for Personal Independence Payment (PIP) said the same.
The charity says the disability benefits system fails to take adequate account of the fluctuating and hidden symptoms of MS, or the extent of their impact. Chief executive Michelle Mitchell said: “Having MS is enough; it should not be made harder by a welfare system that doesn’t make sense for people living with the condition.
“Lack of understanding of the condition and the failure to use information from medical professionals is causing stress or contributing to relapses and deteriorating health. This is counterintuitive to a system designed to support people with disabilities.”
ESA, and its eligibility test, Work Capability Assessments, and PIP have been dogged by controversy. The fairness of the assessments have been called into question repeatedly and there have been severe delays in processing claims, leaving people stressed and penniless while they wait. As well as the detrimental impact on health recorded by the survey, a number of respondents said the changes to the benefits system had forced them to spend less, including on treatment.
Around one in ten said they had reduced outlay on attending hospital appointments and a similar proportion said they had cut down on medical treatment or prescriptions. About a third said they were spending less on food, 28 per cent on transport and 41 per cent on socialising with family and friends. Under the welfare reform and work bill, currently going through the committee stage in the House of Commons, people considered capable of work at some point in the future or of beginning to move into work immediately will see their ESA reduced.
Michelle said: “Living with a chronic, disabling, neurological condition such as MS is hard – it is also expensive. There are often substantial extra costs which add an average of £200 a week to the household bills. Steps must be taken to make sure the disability benefits system is working for those who rely on it or people with MS will continue to struggle.”
A spokesman for the Department of Work and Pensions said: “We understand that going through the assessment process can be difficult for people suffering from conditions such as MS and our staff work hard to make it as straightforward as possible.
“The purpose of an assessment is to identify the support that a claimant needs and they are carried out by registered and experienced health professionals. Our staff receive training and guidance for a range of medical conditions including fluctuating conditions such as MS.”
Between 2013 and 2014, MS-UK experienced a 23% increase in the amount of people who use the MS-UK Helpline, and benefits is one of the top three subjects people contact the Helpline about.
For support today, contact the MS-UK Helpline on freephone 0800 783 0518 or via our live webchat service http://www.ms-uk.org/livewebchat
Source: The Guardian © 2015 Guardian News and Media Limited (14/09/15)
Merck to submit Cladribine for Euro registration (11/09/15)
German healthcare firm Merck has announced it is to submit its investigational treatment Cladribine Tablets for the treatment of relapsing MS for registration in Europe. The decision follows the company’s evaluation of new data and additional analyses of the compound’s benefit-risk profile.
Merck has submitted a letter of intent to the EMA to file a Marketing Authorization Application (MAA) for Cladribine Tablets, which initiates a process to address a number of pre-submission requirements.
“I applaud Merck for its decision to move forward with Cladribine Tablets as demonstrated in its Letter of Intent to the European Medicines Agency,” said Professor Giancarlo Comi, director of the Institute of Experimental Neurology (INSPE) and of the department of neurology at San Raffaele Hospital in Milan, Italy. “This decision is very positive for patients with multiple sclerosis because tailoring treatment to their individual needs is a key strategy for optimizing their care, and to achieve this we need to have access to more therapeutic options. While the options available to treating neurologists have grown over the years, Cladribine Tablets have the potential to offer a truly innovative addition to the armamentarium physicians have at their disposal to treat their patients."
“Time has brought additional data that allows a better characterisation of the benefit-risk profile of Cladribine, and this has driven our decision to move forward with the registration process,” said Belén Garijo, of the executive board of Merck and CEO Healthcare.
Merck wound down its clinical development program for Cladribine Tablets in 2011 after some regulatory authorities expressed concerns over the insufficient characterisation of the drug's benefit-risk profile. Nevertheless, several large clinical trials were allowed to complete and additional safety information was also collected in a long-term registry.
Source: Merck © Merck KGaA, Darmstadt, Germany (11/09/15)
Scientists discover why cognitive speed slows in MS patients (11/09/15)
In the first study of its kind, researchers at the Centre for BrainHealth at The University of Texas at Dallas and UT Southwestern Medical Centre found that individuals with multiple sclerosis (MS) have decreased connectivity between key regions of the brain, slowing their cognitive speed and leading to impairments in concentration, attention, memory and judgment.
The findings have been published in Neuropsychology.
“Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS,” said Dr. Bart Rypma, Center for BrainHealth principal investigator, who also holds the Meadows Foundation Chair at UT Dallas.
“While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter’s importance in human cognitive performance.”
In the study, MS patients, compared to non-MS individuals, showed weaker brain connections between the dorsolateral prefrontal cortex, which is responsible for executing goal-directed thought and action, and posterior brain regions, which carry out tasks related to cognitive speed, such as visual processing, motor execution and object recognition.
Researchers, collaborating with Dr. Elliot Frohman, director of the multiple sclerosis program and clinical center at UT Southwestern, recruited 29 participants with relapsing-remitting MS and 23 non-MS patients. Participants underwent functional magnetic resonance imaging (fMRI) while completing a test of cognitive processing speed.
Participants were given four seconds to view a nine-item key of number and symbol pairs and one number-symbol pair probe. Participants were asked to indicate whether the probe appeared in the key.
While accuracy was similar for both groups, response times for MS patients were much slower. Analysis of the fMRI data revealed that while completing this measure, MS patients showed weaker functional connections with the dorsolateral prefrontal cortex.
“These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain,” said Nicholas Hubbard, the study’s lead author and a doctoral candidate at the Centre for BrainHealth working with Rypma.
“Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required.”
The research supports the need for therapies that target white matter structures and white matter proliferation. Rypma and Hubbard are further exploring the physiology of white matter to better understand cognitive speed reductions not only in MS patients, but also in healthy aging individuals.
Source: UT Dallas News Center © 2015 The University of Texas at Dallas (11/09/15)
Melatonin could help treat MS (11/09/15)
Insomniacs and world travelers alike use melatonin—a hormone that regulates the body’s internal clock—to help them fall asleep and get some extra shuteye. Now, a new study shows that the “sleep hormone” may also give relief to patients with multiple sclerosis.
A possible environmental factor in the cause of MS could be changes in the seasons, says Mauricio Farez, a neurologist at the Raúl Carrea Institute for Neurological Research in Buenos Aires, and after he and colleagues noticed fewer MS flare-ups took place in the fall and winter—the time of year that melatonin production is at its peak.
Melatonin levels depend on sunlight exposure, so seasonal changes cause the hormone to fluctuate; less sunlight in the fall and winter increases melatonin, whereas more sunlight during spring and summer decreases it.
To test the “seasonal” effect of melatonin on MS patients, the researchers monitored 139 MS patients for a year, tracking relapse rates and levels of a small molecule in melatonin called 6-SM. They saw that during fall and winter, patients’ relapse rates were 32 per cent lower than the rest of the year, when melatonin levels naturally dip.
Thinking the immune system likely played a key part, the scientists hypothesised that the increase in melatonin led to an increase in defensive bodies known as T regulatory cells, which work by secreting protective proteins that keep rogue immune cells in check. At the same time, melatonin activates a protein that blocks production of the harmful T cells. The researchers then confirmed their hypothesis in mice: When they dosed the animals with melatonin, the rodents ramped up their production of protective T cells and reduced their concentrations of harmful cells.
The team saw similar effects in in human cells in the lab, reports online today in Cell. “Our research explains something that wasn’t known before in terms of how multiple sclerosis is modulated by the environment,” says co-author Francisco Quintana, a neurologist at the Ann Romney Centre for Neurologic Diseases at Brigham and Women’s Hospital in Boston.
Although the findings are a step in the right direction, the link between melatonin and the immune system still lacks some important details. Researchers have yet to pinpoint, for example, how helper T cells protect the myelin sheath from misguided immune attacks. Farez says he and his colleagues plan to explore that process more in the future.
But other researchers caution against getting too absorbed in one single mechanism of an extremely complicated disease. “This group is enthusiastic about the role of [rogue cell] Th17, and so am I, but it’s only part of the story,” says Lawrence Steinman, a neurologist at Stanford University in Palo Alto, California, who specializes in MS.
Follow-up clinical research should target a larger, more inclusive population, experts say. The current study included only patients from Buenos Aires. Farez says a diverse geographic sample is important to ensure melatonin has the same effects on patients in places with different amounts of seasonal daylight.
But the team’s main concern doesn’t have to do with experimental setup. It has to do instead with the knock-on effects of publishing such research. Melatonin is widely available as an over-the-counter sleep aid, and they worry that some MS patients might use the hormone as a supplemental treatment. “We don’t want patients to see the study and misinterpret our results,” Farez says. “It’s a neat study and great data, but we still need to do a lot of work.”
Source: AAAS Science © 2015 American Association for the Advancement of Science (11/09/15)
Discovery of mechanism that “guides” immune system could help MS research (10/09/15)
In a new study entitled Neutrophil Trails Guide Influenza-Specific CD8+ T Cells In The Airways, researchers have uncovered a key mechanism mediated by neutrophils that guides immune system cells to the site of an injury or infection.
These findings are particularly relevant to the study of autoimmune diseases such as multiple sclerosis, since blocking immune cells from migrating and attacking healthy tissue may disrupt the progression of these conditions.
The study was published in the journal Science.
The influenza virus infects the layer of cells that line the respiratory tract. When infection occurs, cells of the immune system must be able to travel and reach the site of infection to eliminate the infected cells. Crucial players in the immune system for eliminating viruses are effector T cells. However, how these cells are guided and able to reach their final destination, either at the site of an injury or infection, is poorly understood.
In this new research, a team of scientists investigated how effector T cells are guided to the site of infection and discovered that this is achieved with the help of cells called neutrophils – a key player of the immune system and the first cells responding to infections. Neutrophils are the most abundant type of white blood cells of the immune system and are highly motile. The authors observed that neutrophils arrive rapidly (within one hour) to the site of infection and discovered that these migrating cells leave a long-lasting “trail” enriched in a chemokine, CXCL12. Chemokines are small protein molecules secreted by cells to “attract” other cells, in this case the effector T cells. When the team specifically removed the CXCL12 signalling, they discovered that T cells were unable to reach the site of infection so easily and that the ones who did were less efficient.
Minsoo Kim, Ph.D., study lead author and associate professor of Microbiology and Immunology at the School’s David H. Smith Centre for Vaccine Biology and Immunology noted in a news release: “Immune cells team up and share information to get their job done, much like many types of animals take part in collective behaviours to benefit the group as a whole.”
David J. Topham, Ph.D., co-author and the Marie Curran Wilson and Joseph Chamberlain Wilson Professor of Microbiology and Immunology added, “Understanding how immune cells collaborate to arrive at the site of an infection will lead to new ways to control and improve the body’s response to all types of illnesses.”
In multiple sclerosis and lupus, two autoimmune diseases, immune cells migrate and attack healthy tissue. These new findings may also underlie autoimmune disease pathogenesis, and so blocking neutrophil-mediated CXCL12 release may benefit multiple sclerosis and lupus patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (10/09/15)
‘Smoking impacts on multiple sclerosis’ (10/09/15)
Patients with multiple sclerosis are at raised risk of their disease progressing if they continue to smoke, new research suggests.
Cigarette smoking is a known risk factor for multiple sclerosis, according to Dr Jan Hillert of the Karolinska Institutet in Stockholm, Sweden, and colleagues writing in JAMA Neurology. Disease development is 20 per cent to 50 per cent more likely in smokers than non-smokers, "making it a strong avenue for influencing patient outcomes".
Previous studies "have not specifically assessed the period after diagnosis or whether continued smoking affects the disease course", claim the team, so they investigated further. They carried out a study of 728 multiple sclerosis patients who smoked at diagnosis.
Analysis showed that "each additional year of smoking after diagnosis accelerated the time to secondary progressive disease by 4.7 per cent". They add: "Those who continued to smoke continuously each year after diagnosis converted to secondary progressive disease faster than those who quit smoking, reaching secondary progressive disease at 48 and 56 years of age, respectively."
They wrote: "We propose that patients with multiple sclerosis should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating multiple sclerosis-related disability. Health care services for patients with multiple sclerosis should be organised to support such a lifestyle change."
In an editorial, Dr Myla Goldman of the University of Virginia, USA, added: "Even after multiple sclerosis diagnosis, smoking is a risk factor worth modifying."
Ramanujam, R. et al. Effect of Smoking Cessation on Multiple Sclerosis Prognosis. JAMA Neurology 9 September 2015 doi:10.1001/jamaneurol.2015.1788.
Source: Englemed Health News copyright Englemed Ltd 2015 (10/09/15)
New genetic risk factors identified (10/09/15)
Two new risk factors for multiple sclerosis have been identified by a research group at the Wellcome Trust Centre for Human Genetics at the University of Oxford in the United Kingdom.
Led by Dr. Loukas Moutsianas, the team discovered that having key gene allele interactions (each of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome - specifically HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02 in this case )put an individual at risk for developing multiple sclerosis. The findings were outlined in a study published in the prestigious journal Nature Genetics, entitled “Class II HLA Interactions Modulate Genetic Risk for Multiple Sclerosis.”
The research team was working off of previous knowledge that human leukocyte antigen (HLA) alleles — specifically, the HLA-DRB1*15:01 allele — dominate a patient’s risk factor for developing multiple sclerosis. There is some evidence that HLA alleles interact with each other in other neurological disorders, but such a phenomenon had not been reported for multiple sclerosis.
After constructing a model of HLA risk for multiple sclerosis, the researchers were able to create a high-resolution map of HLA risk for the condition. Agreeing with previous literature, the team found that HLA-DRB1*15:01 increased the risk for multiple sclerosis nearly four-fold. There was an additive risk for certain alleles, while other alleles seemed to be protective.
Studies such as this one define additional risk factors for multiple sclerosis that may help identify patients with the disease more accurately than other risk factors. If an individual suspected to have multiple sclerosis had their genes sequenced, they could know if they were indeed at a higher risk for multiple sclerosis and continue with additional diagnostic tests.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (10/09/15)
New study unravels how myelin is repaired (07/09/15)
Japanese scientists have discovered new information about how the myelin sheath is repaired following damage.
The study, titled “Inactivation of Protein Tyrosine Phosphatase Receptor Type Z by Pleiotrophin Promotes Remyelination through Activation of Differentiation of Oligodendrocyte Precursor Cells,” appeared in the Journal of Neuroscience on September 2, 2015.
The symptoms of multiple sclerosis are due to an immune attack on the body’s own myelin. When myelin is lost around nerve cells, this can cause unpredictable loss of movement, sensation, vision problems and feelings of pain. Myelin is made by special nervous system cells called oligodendrocytes. Although it is well-known that myelin can be repaired by oligodendrocytes if it is damaged scientists do not understand the exact repair mechanisms used by these cells. In MS, myelin unfortunately does not appear to be easily repaired, also for unknown reasons.
The researchers, led by Professor Masaharu Noda and colleagues of the National Institute for Basic Biology, wanted to study how myelin is repaired in mice with an experimental form of MS, induced by the myelin-damaging drug cuprizone. They studied both normal mice and genetically-altered mice that lacked protein tyrosine phosphatase receptor type Z (PTPRZ), which is a protein that may cause oligodendrocytes to turn into mature cells, rather than stay in a more immature stage.
Following loss of myelin with cuprizone, the mice that lacked PTPRZ had more myelin repair than the normal mice. The researchers also found that a protein called pleiotrophin (PTN), seemed to be associated with remyelination in the mouse brains, suggesting that it may inactivate PTPRZ. When studied in vitro (in a dish), oligodendrocytes treated with PTN turned into a form that creates new myelin.
Overall, the study suggests that pleiotrophin is secreted by nerve cells when they are damaged and lose myelin, and pleiotrophin then inhibits PTPRZ. This allows oligodendrocytes to create new myelin.
The new understanding of how myelin is formed could provide the basis for new MS treatments, for example, drugs that inhibit PTPRZ or that increase pleiotrophin might be used in the future. Of course, much more research is needed and the investigators will need to find new compounds that act on PTPRZ.
According to Noda “This achievement was made possible by establishing oligodendrocyte precursor cell lines. Pleiotrophin is an endogenous PTPRZ inhibitor, but if synthetic PTPRZ inhibitors were obtained, then effective treatments for multiple sclerosis should become possible. We are currently directing our research in that direction.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (07/09/15)
Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses (01/09/15)
Women with multiple sclerosis (MS) who intended to breastfeed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth compared with women who did not breastfeed exclusively , according to an article published online by JAMA Neurology.
About 20 percent to 30 percent of women with MS experience a relapse within the first three to four months after giving birth and there are no interventions for effective prevention of postpartum relapse. The effect of exclusive breastfeeding on postpartum risk of MS relapse is controversial with conflicting study results.
Kerstin Hellwig, M.D., of Ruhr-University Bochum, Germany, and coauthors analyzed data from 201 pregnant women with MS collected from 2008 to June 2012 with one-year follow-up postpartum in the nationwide German MS and pregnancy registry. Exclusive breastfeeding was defined as no regular replacement of breastfeeding meals with supplemental feedings for at least two months compared with nonexclusive breastfeeding, which was partial or no breastfeeding.
Of the 201 women, 120 (59.7 percent) intended to breastfeed exclusively for at least two months, 42 women (20.9 percent) combined breastfeeding with supplemental feedings within the first two months after giving birth, and 39 women (19.4 percent) did not breastfeed. Most women [178 (88.6 percent)] had used disease-modifying therapy (DMT) agents before pregnancy.
The authors report that 31 women (38.3 percent) who did not breastfeed exclusively had MS relapse within the first six months postpartum compared with 29 women (24.2 percent) who intended to breastfeed exclusively for at least two months.
The authors note the effect of exclusive breastfeeding "seems to be plausible" since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menstruation. The introduction of regular formula feedings or solid food to an infant leads to a change in a woman's hormonal status resulting in the return to ovulation.
The authors note the main limitation of their study was the selection bias inherent to voluntary registries and reflected in the high proportion of women receiving disease modifying treatments.
Source: Science Newsline © Newsline Foundation 2015 (01/09/15)