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MS news archive October 2015

Sprinter Cox disqualified for being one minute late (30/10/15)

Sprinter Kadeena Cox has been disqualified from the IPC Athletics World Championships after she was one minute late to the call room before her T37 200m semi-final in Doha.

Cox, 25, who was expected to add to her 100m gold, delayed her arrival to avoid the Doha sun exacerbating her multiple sclerosis, but organisers said they were enforcing tighter procedures.

"I'm absolutely gutted for Kadeena," said British head coach Paula Dunn.

"This is an incredibly difficult situation for the athlete and her support team. Whilst we feel this is an unduly harsh decision, we will learn from this experience and move on."

Cox, who was a keen sprinter before suffering a stroke and being diagnosed with MS in 2014, and fellow medal contender Mandy Francois-Elie of France were the first athletes to be penalised for this trangression.

Stricter procedures came after the Great Britain team had appealed against the late arrival of American wheelchair racer Alexa Halko to the call room ahead of the T34 100m, which was won by Hannah Cockroft.

Baroness Grey-Thompson, GB Paralympic legend, said: "The biggest loser here is Kadeena. Whatever has happened up to now in the championships, unfortunately this is the ruling and the athlete and coaches and team need to make sure competitors are at the call room at the correct time. It sounds harsh but you have that responsibility.

"Why the competition organisers have waited until day eight to enforce the rule, I don't know. It should have been sorted from day one and it should never have come to this."

International Paralympic Committee communications director Craig Spence told BBC Radio 5 live: "An official communication went to every team on Wednesday night via email and it was posted in the pigeonholes of every single team. There was a reminder that went out on Thursday morning that the rule would be fully enforced.

"One of the teams who complained was Great Britain. The rule has now been enforced and it is Kadeena Cox and Mandy Francois-Elie who have come a cropper unfortunately, but we have to apply the rule."

Source: BBC Sport © British Broadcasting Corporation 2015 (30/10/15)

New finding will help target MS immune response (29/10/15)

Researchers have made another important step in the progress towards being able to block the development of multiple sclerosis and other autoimmune diseases.

Published in the journal Nature Communications, researchers at the University of Adelaide have identified a key protein involved in a 'super-inflammatory' immune response that drives the progression of MS and other autoimmune diseases.

The protein is a specific 'chemokine receptor' involved in moving the body's immune response cells, the T-cells, around the body when they are in the super-inflammatory mode needed to fight persistent infections or conversely, as in the case of autoimmune diseases like MS, attacking the body's own tissues. This chemokine receptor, called CCR2, is a different receptor than was widely assumed to be involved.

"Everybody has been focussing on the CCR6 receptor as the one to target to control this inflammatory response," says project leader Professor Shaun McColl, Director of the Centre for Molecular Pathology at the University of Adelaide.

"We've now shown that the receptor to target is actually CCR2. Blocking CCR6 makes the disease worse. If we can find an antagonist to block the CCR2 receptor specifically on these T-cells, we should be able to control the progression of MS."

The University of Adelaide research was conducted by PhD student Ervin Kara under the supervision of Professor McColl and research fellow Dr Iain Comerford, also in the University's School of Biological Sciences.

Another potential benefit of the research is in making improved vaccines to fight infection.

"Unlike in autoimmune diseases, where the body's immune response is destroying its own cells and the aim is to block T-cell migration, with persistent infection we want to turn on the super-inflammatory response and enhance the migration of the immune cells to sites where they are needed," says Professor McColl.

"This research may help guide development of vaccines that can better force that immune response."

Source: Medical Xpress © Medical Xpress 2011 - 2015, Science X network (29/10/15)

HIV drugs helps multiple sclerosis patient walk again (29/10/15)

A woman has claimed her multiple sclerosis improved so dramatically she was able to walk again after being prescribed HIV drugs.

Shana Pezaro, 36, from Hove, East Sussex, was given antiretroviral drugs after fearing she may have contracted HIV.

Within days, Miss Pezaro noticed an easing of her MS symptoms.

When a doctor saw her walking up a flight of stairs after years of using a wheelchair, he set up a clinical trial.

Miss Pezaro was a dancer and piano teacher before being diagnosed with MS at the age of 28. The condition affected her hands and feet and she used a wheelchair.

About a year ago, Miss Pezaro thought she may have been exposed to HIV and her doctor prescribed emergency antiretroviral drugs.

"Three days after I took the drugs I walked up a flight of stairs," she said.

"That was an unbelievable, massive change."

Prof Julian Gold from the Prince of Wales Hospital in Sydney, saw a video of Miss Pezaro climbing the stairs and a clinical trial was set up to look at the impact of single or combination antiretroviral drugs on MS patients.

An earlier study led by Dr Gold conducted with Queen Mary University, London and the University of Oxford showed an association between HIV and MS.

They reported antiretroviral treatment may suppress other viruses such as those which may cause MS.

Dr Gold said: "The next stage of the investigation is to use a very similar combination [of HIV drugs] that Shana took. I think that might be quite optimistic."

Diet affects progression of autoimmune diseases (27/10/15)

Dietary fatty acids affect the development and progression of autoimmune chronic-inflammatory diseases such as multiple sclerosis, a new report claims.

In a collaborative study between the Departments of Neurology at the Ruhr-Universität Bochum (St. Josef-Hospital) and the Friedrich Alexander Universtiy Erlangen, researchers now found that long-chain fatty acids promote the development and propagation of CNS reactive immune cells in the intestinal wall. On the contrary, short-chain fatty acids promote the development and propagation of regulatory cells in the immune system. Aiden Haghikia and Ralf Linker published their results in the current edition of the renowned journal Immunity.

The research focus within the medical community has increasingly centred on the human intestine and its bacterial population, the so-called microbiome, especially in neurological disorders such as multiple sclerosis. Here, cumulative evidence suggests a considerable influence of the intestinal microbiome on disease emergence and progression. The interaction between intestinal contents and the immune system is influenced by different factors. In particular, diet as an integral part of daily life and the most evident environmental factor has drastically changed in industrialized nations.

In the current study, researchers demonstrated in both the cell culture dish and in an experimental model, that long-chain fatty acids, such as lauric acid, promote the development and propagation of inflammatory cells in the intestinal wall. On the contrary, short-chain fatty acids, first and foremost propionic acid (or its salt propionate), lead to the development and propagation of regulatory cells of the immune system in the intestinal wall. These cells have the capacity to regulate excessive inflammatory responses and autoreactive immune cells.

Interestingly enough, the researchers did not observe any effects of dietary fatty acids once the intestine was entirely germ-free. This suggests that the intestinal microbiome is directly involved in the mechanism of fatty acid action. Further experiments showed that it is rather the metabolic products of the microbiome than a single bacterial strain which is holds responsible for the observed effects.

Today, researchers assume that autoimmune diseases like multiple sclerosis are caused by an imbalance between weakened regulatory and pro-inflammatory autoimmune mechanisms. Still, the large majority of approved immunotherapies aims at weakening or blocking pro-inflammatory components of the immune system. By strengthening regulatory pathways, for example by using propionate as a supplement to established drugs, therapies could be further optimised. The researchers from Bochum and Erlangen now plan to employ the gained insights to develop innovative dietary add-on therapies to established immunotherapies for MS.

Source: Advantage Business Media © Copyright 2015 Advantage Business Media (27/10/15)

Rogue B cells may drive inflammation in MS (27/10/15)

A new study has uncovered a type of B cell that may fuel inflammation in patients with multiple sclerosis. The findings help explain the long-standing question of why an experimental therapy that removes these immune cells from the body is effective against the disease. Selectively eliminating the pool of rogue B cells, while sparing healthy B cells, may offer a more targeted approach for treating multiple sclerosis and potentially other autoimmune disorders, researchers say.

The study appears in the latest issue of Science Translational Medicine.

"It opens up a window into an exciting new biology that we hadn't appreciated before," said senior author Amit Bar-Or of McGill University. "Some [B cells] may be bad in MS and some may actually be beneficial."

The subset of pro-inflammatory B cells may also serve as a potential marker of disease relapse and patients' response to treatment, said Bar-Or.

Multiple sclerosis is traditionally viewed as a T cell-driven disease. In this autoimmune disorder, the immune system, primarily T cells as well as immune cells called myeloid cells, are thought to destroy myelin, a fatty substance that insulates and protects nerve fibres.

B cell depletion therapy, which removes B cells from the blood, can keep relapses at bay in multiple sclerosis patients. The success of this treatment in clinical trials has put the spotlight on B cells as key players in the disease. B cells are best known for their ability to make antibodies, and abnormal antibodies are common in multiple sclerosis patients.

However, the B cell depletion treatment has little effect on the abnormal antibodies found in these patients. This "striking and surprising observation" led Bar-Or and colleagues to suspect functions for B cells beyond antibody production, he said. B cells fulfil other important roles, including secretion of cytokines, small signalling proteins that can either quench or promote inflammation.

Analysing B cells in blood samples from multiple sclerosis patients and healthy individuals, and studying patients' immune responses before and after B cell depletion therapy, Bar-Or's team identified a subpopulation of B cells that releases a powerful pro-inflammatory cytokine called GM-CSF, which is known to drive inflammation in the brain.

Compared to healthy individuals, untreated multiple sclerosis patients had abnormally abundant and more readily activated GM-CSF-producing B cells. These B cells stimulated myeloid cells in a dish to secrete pro-inflammatory cytokines, which in turn can activate pro-inflammatory T cells.

After undergoing B cell depletion therapy, multiple sclerosis patients experienced fewer flare-ups of their symptoms and showed reduced inflammation in their blood. The results suggest that by partially eliminating the rogue B cell pool, the therapy may have blunted inflammation triggered by myeloid cells and T cells. These benefits persisted for months after treatment and even as patients formed new B cells.

While B cell depletion therapy has proven highly effective in advanced clinical trials, its long-term safety remains to be seen. The therapy "may be taking some of the good with the bad, so by getting a better sense of who the bad guys are, we can hopefully develop treatments that are as effective and potentially even safer," said Bar-Or.

Source: American association for the advancement of science © 2015 AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE (27/10/15)

Negative results for Tysabri secondary progressive multiple sclerosis trial (22/10/15)

Biogen has reported negative data from the Phase III trial of natalizumab, in secondary progressive multiple sclerosis. The Phase 3 ASCEND study investigating natalizumab in the treatment of secondary progressive multiple sclerosis (SPMS) did not achieve its primary and secondary endpoints, Biogen reported. During the study, natalizumab was generally well tolerated and adverse events were consistent with its known safety profile.

ASCEND evaluated the efficacy and safety of natalizumab to slow the accumulation of disability progression unrelated to relapse in SPMS patients, an unmet medical need. The majority of study participants had EDSS scores of 6.0 to 6.5 (walking aid required) and were non-relapsing for two years prior to enrollment in the study. The study's composite primary endpoint evaluated the percentage of patients whose disability had progressed on one or more of three disability measurements comprising the composite endpoint.

Natalizumab demonstrated a statistically significant effect on upper limb function (one of the three components of the primary composite endpoint) unrelated to relapses. Consistent with the established effects of natalizumab in relapsing multiple sclerosis, analyses of exploratory endpoints suggest that some patients received a benefit from treatment, including reduction of relapses and new MRI lesions.

"While we're disappointed with these results, we believe this research will provide the MS community important insights into this more advanced patient population, and the benefits that natalizumab may provide in areas such as upper limb function," said Alfred Sandrock, M.D., Ph.D., group senior vice president and chief medical officer at Biogen. "Given the challenges of treating this advanced stage of MS, these results underscore the importance of treatment early in the course of disease with effective disease-modifying therapies before a patient advances to SPMS."

Source: Business Wire © Business Wire 2015 (22/10/15)

Anti-LINGO antibody appears to promote remyelination in optic neuritis (20/10/15)
The investigational monoclonal antibody BIIB033 (Biogen Idec) appears not only to improve optic nerve latency in the affected eye of patients with acute optic neuritis (AON), often one of the first manifestations of multiple sclerosis (MS), but also has an impact on the unaffected eye, new research suggests.

The findings provide valuable information on the efficacy of this monoclonal antibody for remyelination and could mean that this agent has the potential to be the first neuroprotective therapy in this condition.

Results of two parallel studies of the investigational agent were presented here during the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015.

B11B033 is directed against LINGO-1, a central nervous system–specific membrane glycoprotein and suppressor of oligodendrocyte differentiation and myelination.

Optical nerve latency is a measure, in milliseconds (ms), of the time it takes for information to travel between the retina and the visual cortex in the back of brain. "Normally, it takes about 100 ms for that information to travel between these two points," Diego Cadavid, MD, Biogen Idec, Cambridge, Massachusetts, explained to Medscape Medical News in an interview.

Delayed latency of the visual evoked potential (VEP) is a major sequelae of AON. Recovery of VEP latency indicates remyelination.

AON is a common presentation in MS. Most patients with this condition — up to 80% — will eventually be diagnosed with MS.

The RENEW study included 82 patients at 33 sites who received treatment with 1 g of methylprednisolone for 3 to 5 days, had no history of MS, and were experiencing a first unilateral episode of AON with onset within 28 days of the baseline visit.

"This means that the optic nerve on one of the eyes was acutely inflamed with loss of myelin and damage to the axons and neurons, while the other eye — we call it the 'fellow' eye — was normal," explained Dr Cadavid.

These patients were randomly assigned to receive intravenous anti–LINGO-1, 100 mg/kg, or placebo every 4 weeks for 24 weeks.

The primary endpoint was improvement in optic nerve conduction latency by full-fluid (FF) VEP. An electrophysiologic technique routinely used by neurologists in assessing MS, FF-VEP measures latency. It also measures the strength of that information, or the amplitude.

Good Target

"One of the reasons we selected this endpoint was because it's well known that the human brain does not repair these optic lesions well," said Dr Cadavid. "On average, only about 20% of patients recover their latency, so it was a good target to look at for a treatment effect."

There were 69 patients in the study's per protocol (PP) population: 33 in the treatment group and 36 in the placebo group. In this PP population, the study showed that at week 24, the adjusted mean change in FF-VEP was 22.24 ms in the placebo group compared with 14.69 in the treatment group, for an average difference of –7.55 ms (95% confidence interval [CI], –15.12 to 0.01; P = .05).

"The fact that we observed that improvement on average is for us evidence that this drug is biologically active in humans," said Dr Cadavid. "That's something we never had before; we only had data from animal models."

For the intention-to-treat population of 82 patients, the results were less robust. The average between-group difference was –3.48 ms (95% CI, –10.61 to 3.65; P = .33).

At week 32, in the PP population the adjusted mean FF-VEP change was 22.35 ms in the placebo group vs 13.22 ms in the treatment group. Here, the average difference was a reduction of 9.13 ms (95% CI, –16.11 to –2.14; P = .01).

For the intention-to-treat population at 32 weeks, the average difference between the two groups was –6.06 ms (95% CI, –12.66 to 0.53; P = .07).

Further analysis showed greater latency in older patients. "We found that pretty much all the benefit from anti-LINGO was observed in the half of patients who were older, mean age 38 years, while the other half who were younger, mean age 25 years, seemed to recover on their own," commented Dr Cadavid.

In MS, it's clear that there's a failure of remyelination, but experts don't all agree on why this is, he added. "One theory blames it on aging; as we humans age, we lose the ability to repair."

Patients who were enrolled in the study earlier during the 28-day "window" from first symptom to first dose also seemed to do better, said Dr Cadavid. "People who received the dose on average during the third week vs the fourth week seemed is have a greater benefit." As well, those with more severe baseline visual acuity impairment also did better.

Dr Cadavid stressed that these subgroup analyses are "hypothesis-generating" only.

Parallel Study

In a separate paper, the researchers carried out a parallel multifocal (MF)-VEP substudy analysis of the fellow unaffected eye in 39 patients from the RENEW study: 18 in the placebo group and 21 in the anti–LINGO-1 group. MF-VEP, which covers a significantly larger area of the visual field, with each segment producing a different result, is better than FF-VEP for measuring amplitude changes.

For this analysis, researchers followed the "fellow" or normal eye visual pathway over 8 months. The change in MF-VEP amplitude at week 32 in the placebo group was –31.407 vs 1.926 in those receiving anti-LINGO, for an estimated difference of 33.333 (95% CI, 16.408 - 50.258; P =.004).

"We made a very interesting observation; the group randomized to placebo experienced a steady and gradual loss of amplitude — the strength of the signal," commented Dr Cadavid. "Within 8 months, this population was already having a measurable loss of amplitude."

This is important as this population "is as early as you can catch any patient with MS," he said.

Equally important, he added, was the observation that the group randomly assigned to anti-LINGO did not experience that loss.

The new research provides two important findings, said Dr Cadavid.

"First, that very early into the disease, even before patients could formally be diagnosed with MS, the brain, specifically the visual pathway, is experiencing damage. Second, that the group randomized to anti-LINGO appears not to have experienced that damage, so it's either being protected or being rapidly repaired."

Researchers are now carrying out another study — SYNERGY — that is testing four doses of the agent (3, 10, 30, and 100 mg/kg) and placebo in patients concurrently taking an anti-inflammatory treatment.

"We believe this will provide us with valuable information regarding the potential of anti-LINGO to hopefully one day help MS patients," said Dr Cadavid.

The study is fully enrolled, with results expected next year, he said.

The RENEW study was supported by Biogen. Dr Cadavid is an employee of and stockholder in Biogen.

Reference: Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015. Abstracts 165 and 231. Presented October 9 and 10, 2015.

Source: Medscape Multispeciality Copyright © 1994-2015 by WebMD LLC (20/10/15)

High intake of plant-based fatty acids may lower MS risk (15/10/15)
Eating walnuts and cooking with canola oil may be the next trend in reducing the risk of developing multiple sclerosis (MS), a new study presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) suggests.

Investigators have found people who consumed the most foods containing plant-based polyunsaturated fatty acids (PUFAs) had the lowest MS risk. However, they found no significant association between consuming a diet high in fatty acids from fish and MS risk.

That plant-based, not fish-based, PUFAS were linked to MS came as something of a surprise, lead researcher Kjetil Bjørnevik, MD (PhD student), research fellow, University of Bergen, Norway, told Medscape Medical News.

"For the last half a century, there has been a lot of interest in PUFAs, but it has been mainly focused on fish-derived PUFAs — what we get from consuming fish. Here in our study, we don't actually see an association between those types of PUFAs and MS risk."

The study was presented here at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015.

PUFAs are fatty acids that contain more than one double-bond in their backbone. It's believed that they have immune-modulatory, anti-inflammatory, and antioxidant properties.

Dietary intake of fatty acids has been an area of research interest in MS for several decades. Back in the 1950s, some studies suggested that people who ate lots of fish had a lower risk for MS.

Over the years, case-control studies suggested that intake of both foods rich in PUFAs (eg, fatty fish, such as tuna and salmon) and those rich in isolated PUFAS (eg, cod liver oil) was associated with lower MS risk.

A recent study showed an inverse association between MS and overall intake of the PUFA omega-3, particularly from fish-derived fatty acids.

"This fish-based hypothesis has been around for a long time, but now we're seeing new hypotheses. For example, some people think the lower risk is due to vitamin D intake, which is also a very hot topic," said Dr Bjørnevik.

And now another new area of interest could be PUFA-rich plants.

For the study, investigators used the large databases of the Nurses Health Study (NHS; 1984-2004) and the NHS 2 (1991–2009). Together, researchers prospectively followed 177,209 women who did not have MS at baseline, beginning in 1984 for NHS participants and 1991 for NHS 2 participants.

Using a validated food-frequency questionnaire, researchers queried all study participants about their dietary habits every four years. For dietary fat, they looked at intake of total fat, saturated fatty acids, and monounsaturated fatty acids as well as PUFAs. During follow-up, 479 participants were diagnosed with MS.

For all dietary fat categories, the hazard ratio (HR) for the top quintile of intake compared with the bottom quintile in both the NHS and NHS2 was below 1.0, suggesting a lowered risk for MS. The HR was lowest for PUFAs.

This was after adjustment for age, ethnicity, latitude at age 15 years, body mass index at age 18 years, years of smoking, vitamin D supplementation, and total energy intake.

The study results suggest PUFA intake from plants was driving the association. The MS risk for α linolenic acid was significantly lower in the highest vs lowest intake groups. The HR was also lower for intake of linoleic acid in this high-intake group.

"We see that those people who get PUFAs from a plant-based diet, for example from vegetable oils, have a lower risk," said Dr. Bjørnevik. "This is surprising because it's not something we have seen earlier."

In addition to walnuts and canola oil, foods rich in these plant-based PUFAs include flax seeds and linseed oils, said Dr Bjørnevik. PUFAs are not found in high amounts in olive oil, which contains a different type of fatty acid, he said.

But contrary to popular belief in some circles, there was not a significant association between high intake of fish-based PUFAs and lowered MS risk in the study. The effect estimates for docosahexaenoic acid and for eicosapentaenoic acid were close to one, indicating no association with MS risk.

Results of an analyses using the cumulative average intake of PUFAs during follow-up were similar.

It's impossible to determine from this study how much plant-based PUFAs one needs to consume to lower MS risk. "We just saw that those who ate the most had the lowest risk," said Dr. Bjørnevik. "It's one of the first studies showing this so it's hard to quantify a specific amount."

He emphasised that because this is the first study uncovering this association, "you have to interpret it with caution and it needs to be replicated."

As well, he said, experts can't determine from the study whether plant-based PUFA intake has any benefits, for example disease-modifying effects, on the course of the disease. "It's an interesting finding, but it's very preliminary."

Session co-chair Gilles Edan, MD, professor, clinical neurology and chair, Department of Neurosciences, University Hospital of Rennes, France, said that although he's not a PUFA expert, he found Dr. Bjørnevik's presentation "clear and rather convincing" and that the study was "well designed."

However, examining in detail the quality of scientific data will have to wait until the study is published in a peer-reviewed journal, he said.

Source: Medscape Multispeciality Copyright © 1994-2015 by WebMD LLC (15/10/15)

Rituxan: Don't count it out as MS treatment (13/10/15)
Numerous presentations at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting made it plain that the anti-CD20 biologic drug ocrelizumab may not have the field to itself, if and when it is approved for marketing.

That's because, as those presentations demonstrated, there is an anti-CD20 drug already available and in use at numerous MS clinics in the U.S., and showing results that compare favourably with the phase III data on ocrelizumab also reported here.

That competing older drug is Rituxan.

Researchers involved in the ocrelizumab trials say they think the newer agent will eventually prove to be superior - it is a humanized monoclonal antibody whereas Rituxan is chimeric, and infusion reactions and anti-drug antibody responses may be lessened with ocrelizumab (although this remains to be proven). But clinical reports on Rituxan in patients with both relapsing-remitting and progressive forms of MS indicate the drug is both highly effective and well-tolerated.

For example, among 36 patients with secondary progressive MS given Rituxan at University Hospital Basel in Switzerland, the risk of confirmed progression was cut by nearly 80 per cent compared to conventionally treated patients.

At the University of Colorado in Denver, records for 313 patients treated with Rituxan since 2007 (including relapsing-remitting [RR], primary progressive [PP], and secondary progressive [SP] MS) indicated that relapses were abolished in all but five patients, and only seven subsequently showed new T2 lesion activity. About 20 per cent had mild infusion reactions and 23 per cent developed urinary tract infections.

Experience at three MS referral centres in Sweden, where more than 900 patients have received Rituxan since 2008 (about two-thirds RRMS, one-third PP/SPMS), included annualised relapse rates of 0.04 in RRMS patients and 0.03 in PP/SPMS. Rates of gadolinium-enhancing lesions in the two groups were 0.05 and 0.02 per year, respectively.

Another Swedish review, covering 256 patients who switched from Tysabri to Rituxan or the oral drug Gilenya because of JC virus positivity, found rates of relapse and new MRI lesion activity were markedly lower in those taking Rituxan. Moreover, about 30 per cent of those switching to Gilenya stopped the drug within two years, versus less than five per cent of those moving to Rituxan.

Without marketing approval in MS, payment for Rituxan depends on patients' ability to pay and/or the whims of insurers or the manufacturer (which has reportedly provided the drug to some patients at deep discounts).

Ludwig Kappos, MD, of the University Hospital Basel, told MedPage Today that payment issues would dictate the extent to which Rituxan will continue to be available as an option in MS.

Rituxan currently costs about $30,000 a year as a treatment for rheumatoid arthritis, an FDA-approved indication, with two 1,000-mg doses 14 days apart. The dosing schedules reported with off-label use for MS have been similar.

That cost is considerably less than for other MS drugs, if estimates reported earlier this year in Neurology are accurate. That report indicated that first-generation treatments, including interferon-beta and Copaxone, now run about $60,000 per year, and newer agents even more.

It's currently unknown what ocrelizumab will cost, if and when it is approved. But there may be more to the competition than price: in ocrelizumab's phase III trial for primary progressive MS, ORATORIO, risk of confirmed 12 and 24-week disability progression was reduced by about 25 per cent compared with placebo, and its effect on time to complete a 25-foot walk was similarly modest. Ocrelizumab's performance was more impressive in the trials involving relapsing-remitting MS.

If ocrelizumab isn't perceived as more effective than Rituxan, that may influence insurer's decisions on reimbursement.

Source: MedPage Today © 2015 MedPage Today, LLC (13/10/15)

Fifteen-year follow-up study of Rebif patients published (13/10/15)
EMD Serono, the American biopharmaceutical business of Merck KGaA, Darmstadt, Germany, has announced that the Journal of Neurology, Neurosurgery and Psychiatry (JNNP) has published 15-year follow-up data for Rebif, the company's high-dose, high-frequency beta interferon for relapsing-remitting multiple sclerosis (RRMS), from the PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) trial.

The published data highlights outcomes from an exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) beta-1a treatment and other possible prognostic factors with clinical outcomes in RRMS.

"The publication of the PRISMS-15 study in JNNP offers the MS medical community a retrospective single visit assessment in a subset of RRMS patients from the PRISMS trial with varying exposure to Rebif," said Dr. Rick Munschauer, Vice President, Medical Affairs, Neurology and Immunology, EMD Serono.

In addition to Rebif, EMD Serono is engaged in strategic research collaborations funding promising neurology research with leading academic and healthcare institutions. The company also has ongoing MS clinical study programs, including a Phase I study of ATX-MS-1467, an investigational therapy for relapsing remitting multiple sclerosis (RRMS), and a Phase IIb study of imilecleucel-T, an investigational therapy for Secondary Progressive MS (SPMS), an area of high unmet medical need. The company has an option agreement with Opexa Therapeutics, Inc. for the development and commercial licensing of imilecleucel-T.

Kappos L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–6. doi:10.1136/jnnp-2014-310024

Source: PR Newswire Copyright © 2015 PR Newswire Association LLC (13/10/15)

Study opens new doors to neuropathic pain treatment research (13/10/15)
Chronic pain results from disease or trauma to the nervous system. Damaged nerve fibres with heightened responses to normal stimuli send incorrect messages to pain centres in the brain. This phenomenon, called "peripheral and central sensitization" is one of the key mechanisms involved in the condition which touches people with diabetes, cancer, and those living with multiple sclerosis.

A new study, published in the September issue of The Journal of Neuroscience, has now provided fresh insight into the role of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which control the transmission of pain signals to a particular region of the brain, the anterior cingular cortex (ACC), identified as the most consistently stimulated region in pain processing.

"We were able to show that reducing hyperexcitability of the ACC by blocking the HCN channels had analgesic effects - basically the feelings of pain were dramatically decreased. Our study has revealed one important mechanism linking chronic pain to abnormal activity of the ACC and it provides a cellular and molecular explanation for the overstimulation of neurons in the prefrontal cortex. This gives us new perspectives on therapeutic strategies that could target the HCN channels to help relieve chronic pain," said Dr. Philippe Séguéla, professor in the department of neurology and neurosurgery and senior author of the study.

Recent neuroimaging studies investigating the role of the prefrontal regions of the brain in neuropathic pain have shown how emotional, psychological and cognitive factors can influence pain perception.

"The ACC has been shown to be a key centre to cognitive functions linked to memory and affective functions involved in feelings and emotions. We know that patients who suffer from chronic pain experience impairment of their working memory, difficulties focusing on certain tasks and may suffer from depression and anxiety. Our findings open new doors to research possible treatment of these debilitating symptoms that are linked to chronic pain." said Dr. Séguéla.

Source: News-Medical.Net Copyright 2000-2015 AZoM.com Limited (13/10/15)

Single drop of blood in brain can activate autoimmune response (12/10/15)
A new study from the Gladstone Institutes shows a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS). This is the first demonstration that introduction of blood in the healthy brain is sufficient to cause peripheral immune cells to enter the brain, which then go on to cause brain damage.

A break in the blood-brain barrier (BBB) allows blood proteins to leak into the brain and is a key characteristic of MS. However, it was unclear whether the BBB disruption caused the autoimmune response or resulted from it.

In the current study, published in Nature Communications, the scientists created a new animal model of disease to determine if BBB leakage can cause autoimmunity. They discovered that injecting just one drop of blood into the brain set off the brain's immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibres in the brain, and it is the primary site of injury in MS. Scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.

"These findings offer a completely new way of thinking about how the immune system attacks the brain - it puts the blood in the driver's seat of the onset and progression of disease," says senior author Katerina Akassoglou, PhD, a senior investigator at the Gladstone Institutes and professor of neurology at the University of California, San Francisco. "This opens up the possibility for new types of therapies that target blood coagulation factors, upstream of autoimmune processes."

Fibrinogen activated the brain's immune cells, called microglia, and caused them to send out signals summoning peripheral immune cells from other parts of the body to the brain. When these peripheral immune cells--macrophages and T cells--entered the brain, they attacked myelin.

"Our results provide the first evidence that blood promotes T cell responses against the brain," says first author Jae Kyu Ryu, PhD, a staff research scientist at the Gladstone Institutes. "Not only did we confirm that the presence of blood in the brain recruits peripheral immune cells to the area, which is sufficient to cause myelin destruction, we also identified fibrinogen as the critical protein driving this process."

To confirm their findings, the scientists deleted the fibrinogen receptor (complement receptor 3 or CD11b/CD18) on microglia, thereby preventing fibrinogen from activating the cells. Inhibiting this interaction blocked the autoimmune process, stopping the microglia from signaling to the peripheral immune cells and averting myelin damage and inflammation. The researchers are now attempting to block fibrinogen using biological and small-molecule approaches as potential new therapies to suppress autoimmunity directed against the brain, dampening inflammation caused by microglia and T cells.

"These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages," says Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper. "This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells."

The scientists say that having a model of blood-induced brain inflammation is a valuable tool, as it can be used to screen new drugs. These mechanisms may occur not only in autoimmune disorders, but also in other brain diseases that involve inflammation or a break in the BBB, including traumatic brain injury, stroke, Alzheimer's disease, and other dementias.

Source: News-Medical.net Copyright 2000-2015 AZoM.com Limited (12/10/15)

Antibiotic may block conversion to MS (12/10/15)
After a first demyelinating event, a broad-spectrum tetracycline antibiotic may prevent conversion to multiple sclerosis (MS), researchers have claimed.

In a phase III multicenter Canadian study, patients randomised to minocycline had a significant 44.6 per cent relative risk reduction in progressing to MS over 6 months, reported Luanne Metz, MD, of the University of Calgary, at the European Committee for the Treatment and Research in Multiple Sclerosis.

"We feel this should be considered a treatment for MS," Metz said. "If you treat people with a simple prescription, you don't need to do complex paperwork or get insurance going. It's a well tolerated drug that requires no safety monitoring whatsoever."

She said she believes a typical regimen of the drug would cost $500 to $600 annually in Canada (about £250 to £300).

Current therapies work better if they're given to patients soon after their first clinical demyelinating event. However, health and insurance coverage for therapies varies by country and region, which may result in treatment delays until patients have a second clinical attack.

In addition, currently available oral therapies may not be ideal because of safety concerns.

Minocycline is an oral antibiotic with a recognizsd safety profile, widely available, and can be obtained in a lower-cost generic formulation, Metz said, and has many immune-modulating properties.

Preclinical and preliminary clinical studies suggest minocycline may be a therapeutic option in MS, both as a monotherapy and as an add-on to treatment, she added.

Her group enrolled 142 patients, with a mean age of 35.8, who had their first demyelinating event no more than 180 days before enrolment, and had at least two T2 hyperintense lesions on a brain MRI.

The majority of patients (68.3 per cent) were women, the onset was monofocal in 76.8 per cent, and the median expanded disability status scale (EDSS) score was 1.5.

Patients were randomised to placebo or to 100mg of oral minocycline twice a day, and were treated for 24 months or until they developed MS.

The primary outcome was the proportion of participants who developed MS by six months.

Overall, Metz and colleagues found the risk of conversion to MS within six months was 61.4 per cent in the placebo group compared with 34 per cent in the minocycline group -- making for a relative risk reduction of 44.6 per cent and an absolute risk reduction of 27.4 per cent.

The number needed to treat (NNT) was four patients, they added.

By one year, the absolute risk reduction was 25.1 per cent and the relative risk reduction was 37.6 per cent. The NNT remained four, they reported.

Findings at two years weren't significant, but Metz said the study was underpowered to detect a difference at this point in time.

She added there were no unexpected safety issues.

Metz concluded that minocycline can reduce conversion to MS, and should be considered for initial treatment as well as for combination therapy trials, given both its safety and low cost.

"This is exciting because it's oral, it's low cost, and we have lots of safety data," Dennis Bourdette, MD, of Oregon Health & Science University in Portland, told MedPage Today. "It would be a good alternative for CIS [clinically isolated syndrome]."

Bourdette was not involved in the study.

"We have a lot of CIS patients who don't want to go on anything yet, particularly the expensive drugs which are either injectable or oral but have side effects," he added. "Some of those patients prefer to just be followed. But if you could put them on minocycline, you'd still follow them and then if they break through, you can give them something else."

John Corboy, MD, of the University of Colorado Denver, who also wasn't involved in the study, agreed minocycline could be a useful tool for early disease.

"We've talked about this for years, but this is the first large study to show that it works," Corboy told MedPage Today. "It's cheaper than dirt and, if it works and has a durable effect, you could throw this in the drinking water."

Source: MedPage Today © 2015 MedPage Today, LLC (12/10/15)

Vitamin D supplements ‘improve cognition’ (12/10/15)
Patients with multiple sclerosis who were given vitamin D supplements showed improved cognition at three months, a new study shows.

The results suggest that patients with MS should get their vitamin D levels checked and, if deficient, take vitamin D supplements, said Hala Darwish, PhD, a neuroscience expert whose research at the American University of Beirut (AUB) focuses, among other things, on cognitive and inflammatory changes associated with aging.

"I'm one of those who believes that MS patients should take supplements," Dr Darwish told Medscape Medical News.

She presented results of the study here at the Congress of the European Committee for Treatment and Research in MS (ECTRIMS) 2015.

Vitamin D, which can be obtained through exposure to the sun or fortified foods, plays a role in the pathogenesis of MS, said Dr Darwish. It has been shown to improve physical function and decrease inflammation. Evidence also links vitamin D to cognitive performance in older adults.

“We know there are vitamin D receptors in the brain" of both animals and humans, said Dr Darwish. "This suggests a function in cognition."

For the study, researchers recruited adult patients with MS from the AUB centre who were being treated with beta interferon. From blood tests, they determined that 88 patients qualified for inclusion in that they had normal serum 25-hydroxyvitamin D (25[OH]D) levels or were vitamin D deficient.

Researchers collected demographic data, health history, and information on lifestyle habits. They assessed depression and anxiety using the Arabic-Hopkins Symptoms Checklist.

The low and normal vitamin D groups were similar in terms of marital status, income, and employment level. Dr Darwish noted both groups were highly educated, with many having at least a college degree.

As for lifestyle, those with low vitamin D engaged in less physical activity than the normal vitamin D group, and they smoked more and drank more alcohol. This low vitamin D group also tended to participate in fewer leisure activities.

Disease duration did not differ between the groups, but there was a significant difference on the Expanded Disability Status Scale (EDSS), with those in the low vitamin D group having a higher mean score.

This, said Dr Darwish, might explain their differences in physical activity and being less involved in playing online video games.

Study patients were given a battery of cognitive tests, including the Montreal Cognitive Assessment; Symbol Digit Modalities Test (SDMT); Stroop test; and Brief Visuospatial Memory Test Revised (BVMT-R), immediate (10 and 30 seconds), and delayed recall (DR) (20 minutes).

All the cognitive tests were short and altogether took about 45 minutes to complete. In some cases, researchers used the Arabic version of these tests for the first time.

At baseline, the low vitamin D group scored lower on all cognitive tests except the Stroop test. The difference was significant for SDMT and BVMT-DR.

The low vitamin D group was given high doses of vitamin supplements (10,000 IU daily or 50,000 IU per week) for three months. The normal vitamin D group received usual care.

Patients kept a diary documenting sun exposure and vitamin D intake.

After three months, serum 25(OH)D levels in the low vitamin D group increased. The normal vitamin D group also increased, but by much less. The difference between the normal and low vitamin D groups remained statistically significant.

Three months may not be long enough to show statistically significant differences in some test performances, according to Dr Darwish. Additional follow-up studies using more established and validated cognitive tests are needed, she said.

A multivariable analysis showed that, as expected, age was a predictor of cognitive performance for all cognitive tests at baseline and at three months. As well, more years of education predicted cognitive performance on the Stroop test and BVMT at baseline and the STMT at three months.

Vitamin D levels predicted better performance on the BVMT-DR after adjustment for disease duration, EDSS score, age, education, physical activity level, smoking status, alcohol intake, leisure activities, anxiety, and depression.

A higher anxiety score predicted a lower score on the SDMT. Cognitive performance and anxiety in MS seem to be affected by low vitamin D level and improve after vitamin D replacement, said the authors.

Alcohol intake predicted a better cognitive score on the SDMT at baseline and at three months and the BMT-T1 at three months. This association needs further exploration, said Dr Darwish.

Although she didn't attend the presentation, Luanne Metz, MD, a neurologist and professor, clinical neurosciences, University of Calgary, Alberta, Canada, said the study's findings aren't surprising.

"One things that vitamin D does is increase a number of factors, including growth factors, and one of these is BDNF [brain-derived neurotrophic factor], which we know plays a role in cognition as well as inflammation."

At her own clinic, one of the first things patients with MS are told to do is start taking vitamin D supplements at a recommended dose of 4000 to 5000 IU a day. For Canadian patients with MS, "there's no point" in even getting serum vitamin D checked because almost all will have low levels, she said.

The study was funded by the AUB Medical Practice Plan and the Lebanese National Center Research. Dr Darwish has disclosed no relevant financial relationships.

Source: Medscape Multispeciality Copyright © 1994-2015 by WebMD LLC (12/10/15)

No conclusions over best drug for MS (12/10/15)
Two studies - one from France, the other from Denmark - came to conflicting conclusions about whether Tysabri or Gilenya offers better efficacy, researchers have reported here.

The French study, totalling about 630 patients, found relapse rates to be lower with Tysabri, while the Danish study of about 1,200 patients found similar relapse rates in both groups.

Both studies were reported during an oral session at the ECTRIMS meeting in Barcelona, Spain.

"Different findings are not unusual, particularly when it comes to this phase IV stage when one no longer has a perfectly randomised controlled situation," David Miller, MD, of University College London, who was not involved in the study, told MedPage Today, adding convenience and safety should be a high priority when choosing between treatments.

Both Gilenya and Tysabri are approved for relapsing-remitting MS patients and are among a series of treatments for MS that have been approved in recent years.

However, few head-to-head comparisons and no randomised controlled comparisons of the safety and efficacy of these drugs have been done.

There have been some observational data, but the findings are mixed. Indeed, two other recent studies -- one by Braune et al in the Journal of Neurology in 2013 and the other by Kalincik et al in Annals of Neurology this year -- came to similarly conflicting results. The Braune trial found no difference between the two drugs over one year, while the Kalincik paper found higher relapse rates with Gilenya.

The French and Danish registry studies presented at ECTRIMS sought to further clarify the issue.

The French trial, presented by David Laplaud, MD, of CHU Nantes and Inserm in France, assessed clinical and MRI outcomes for relapsing-remitting MS patients from 27 specialised treatment centres, collecting data on 326 patients treated with Tysabri and 303 treated with Gilenya.

They used two methods to control for differences in the populations: multivariate logistic regression and propensity score method based on the inverse probability of treatment weighting. These analyses attempted to control for five factors: gender, number of relapses in the previous year, presence of gadolinium-enhancing lesions, EDSS scores, and hospitalizations.

They found in the multivariate model that those on Gilenya had a significantly higher risk of relapse, new gadolinium-enhancing lesions, and new T2 lesions at two years compared with those on Tysabri.

They saw a similar increase in the risk of having at least one relapse, having at least one gadolinium-enhancing lesion, and at least one new T2 lesion at two years with Gilenya using the propensity score method.

Laplaud acknowledged the study was limited by a lack of randomisation and potential confounders that weren't taken into account, but he still concluded that the study provides class IV evidence that Tysabri has better efficacy than Gilenya over two years.

The Danish study, presented by Nils Koch-Henriksen, MD, of the University of Aarhus in Denmark, assessed all Danish patients who started Tysabri or Gilenya in 2011 or later (Gilenya was approved that year, and Tysabri was already on the market).

In their initial analysis, they assessed 1,201 relapsing-remitting MS cases - 531 on Tysabri, 670 on Gilenya - and found a significant "but probably false difference" in relapse rates that favored Gilenya.

But then they deployed propensity score matching to diminish the amount of confounding in the population, ending up with 942 patients.

In that analysis, they found annualised relapse rates were essentially the same, with no statistically significant difference between groups.

A Kaplan-Meyer analysis found similar probabilities of remaining relapse-free over three years for patients in both drug groups.

Koch-Henriksen noted that using propensity matching was useful for reducing bias in this type of analysis, and concluded that there was "no difference, not even a trend, between the disease activity in Tysabri and Gilenya treated relapsing-remitting MS patients."

"This study could not support that any of the two second-line treatments should be superior to the other," he said during the presentation, adding that convenience and safety should be a high priority when choosing between the two treatments.

Ari Green, MD, of the University of California San Francisco, who wasn't involved in the trial, noted several limiting factors for interpreting the results, including the fact that there may be differences in the way the drugs are used and in patient selection between France and Denmark.

"Clearly they both can't be right," Green told MedPage Today. "However, resolving which one is ultimately correct may be difficult. The size of the studies is not an explanation, as larger studies would tend to find effects that smaller studies lacked the power to detect. However, in this case the smaller study found a difference and one which was large enough that if it were true, should be seen in other studies."

Source: MedPage Today © 2015 MedPage Today, LLC (12/10/15)

Rapid assessment tool “useful” for MS evaluation (12/10/15)
A free screening tool may help clinicians better document and manage their multiple sclerosis (MS) patients' symptoms, according to data presented at the European Committee for Treatment and Research in Multiple Sclerosis Congress in Barcelona.

Ilya Kister, MD, of NYU Langone Medical Center, and colleagues developed the symptoMScreen tool to help clinicians rapidly assess MS symptom severity and in turn improve patient-clinician communication and symptom management. The single-page test includes a battery of seven-point Likert scales for 11 domains commonly affected by MS: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, spasticity, body pain, depression and anxiety. The researchers sought to validate symptoMScreen against Performance Scales (PS) commonly used to evaluate MS symptom severity.

In all, 280 patients with MS completed both the symptoMScreen assessment and PSs. Composite symptoMScreen score correlated strongly with combined PS score and symptoMScreen subscores correlated strongly with criterion measures of respective PS, demonstrating excellent criterion and construct validity.

“It takes approximately one minute for patients to complete, and can help clinicians to better document, understand, and manage their patients' symptoms,” the authors concluded, noting that the screening tool is currently available for free for use by clinicians and researchers.

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc. (12/10/15)

New three-times-a-week Copaxone regimen ruled safe (12/10/15)
A Satellite Symposia entitled Discovering A New World In MS presented by Teva Neuroscience has been held at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.

Dr. Omar Khan, an expert in multiple sclerosis (MS) and related diseases, from the Wayne State University School of Medicine in Detroit, Michigan presented his work under the title Translating The Glatiramer Acetate 40mg three-times-a-week Trial Data Into Real-Life Clinical Experience. The presentation focused on the balance between the risks and the benefits of emerging treatment options for MS, paying special attention to Copaxone.

The U.S. Food and Drug Administration (FDA) and the European Medicine Agency (EMA) approved 20 mg subcutaneous once-daily Copaxone for the treatment of relapsing-remitting multiple sclerosis (RRMS) almost two decades ago, and it remains one of the most widely used disease modifying drugs (DMDs) in the treatment of the MS.

Copaxone 20mg has a good long-term safety profile, however patients see self-injecting and injection-site reactions as a serious inconvenience of the drug.

“Injection site reaction is the most frequent adverse event” said Dr. Khan in his presentation. This side effect can result in non-compliance with the treatment.

With the purpose of improving compliance and reducing injection-site reactions, Copaxone was developed in a high-concentration formulation of 40mg to be administered three-times-a-week.

In a randomised, phase III clinical trial called GALA, researchers found taking Copaxone 40mg three-times-a-week was able to significantly reduce the annualised relapse rate and MRI-disease activity in RRMS patients when compared to a placebo.

The team found the incidence of injection-site reactions in RRMS patients under the 40mg regimen was approximately 20 to 50 per cent less in comparison to patients under a 20mg regimen or 40mg once a day. These findings were confirmed in a phase IIIb trial (GLACIER), where a reduction of 60 per cent in moderate to severe injection-site reactions was observed with Copaxone at 40mg three-times-a-week compared to 20mg once a day. Furthermore, patients reported that the 40mg three-times-a-week regimen was more convenient than the daily regimens.

Copaxone 40mg three-times-a-week has been available in the U.S. for over a year and was recently approved in Europe. It is estimated that in the U.S., more than two-thirds of MS patients currently under Copaxone treatment are in a 40mg three-times-a-week regimen.

“40mg three-times-a-week allows for an increased patient adherence,” concluded Dr. Khan, who believes this Copaxone treatment regimen “is a safe and effective initial treatment option for RRMS patients. In addition, it offers a tailored approach to RRMS patients preferring a less frequent injection schedule for improved convenience of use and a reduced risk of injection-site reactions.”

Source: Multiple Sclerosis News Today © BioNews Services, LLC (12/10/15)

‘No association between MRI measures and PPMS’ (12/10/15)
Results from clinical trials that included patients with relapsing-remitting multiple sclerosis (RRMS) do not appear to be consistent for patients with primary progressive multiple sclerosis (PPMS), according to Markus W. Koch, MD, from the University of Calgary in Alberta, Canada.

“For this study, we wanted to see how MRI measures that we often use relate to clinical outcomes,” Koch said during a session at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.

Previous research on MRI measures in patients with RRMS do not match those with PPMS. “Although MRI measures are often used in PPMS trials, their association with clinical outcomes remains uncertain,” Koch noted.

Patients collected from the PROMiSe dataset underwent MRIs at baseline and then yearly. Confirmed disability progression (CDP) was identified at 12 and 24 months using the Expanded Disability Status Scale (EDSS) and Timed 25-Foot Walk (T25FW), with a three-month confirmation period.

MRI predictors were the presence of gadolinium-enhancing lesions (Gd+) and brain fraction (BF), the inverse of the normalized cerebrospinal fluid volume. Lesion volume (LV), the sum of T1 and T2 lesion component volumes, was also used as a measure.

The outcomes revealed that a significant amount of people had disability progression. The EDSS determined that it rose 19.8 per cent after 12 months and 30.1 per cent after 24 months. The T25FW also showed increasing results with 29.7 per cent disability progression after 12 months and 43.3 per cent after 24 months.

“Baseline EDSS and T25FW were associated with CDP at 12 and 24 months in all models,” Koch verified.

At baseline, 14 per cent of patients had lesions and that percentage did not change very much over time. Brain volume, on the other hand, had an average loss of 2.5 per cent after two years.

“Interestingly though, neither lesion load or brain volume is associated with disease worsening,” Koch divulged. Meaning that the change in lesion load and brain volume did not influence the risk of CDP. However, factors that did predict worsening disability progression was age and being male both one and two years into the study.

These findings indicate that unlike RRMS, there is not an association between MRI measures and PPMS disability progression. At the end of the presentation, an audience member asked if the failed association could have something to with the available imaging tools.

“We definitely need better imaging in the spinal cord,” Koch concluded.

Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC. (12/10/15)

Discovering a ‘new world’ in MS through Genomics (12/10/15)
A Satellite Symposia entitled Discovering A New World in MS supported by Teva Neuroscience has been held at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), currently taking place in Barcelona, Spain.

Prof. David Brassat from the University of Toulouse III, France, gave a talk entitled Genomics: Potential For Navigating Therapy To The Individual Patient. Prof. Brassat has been involved in the search for biomarkers for the different aspects of multiple sclerosis (MS), including genetic susceptibility, prognosis, disease course and response to therapies.

Disease-modifying drugs (DMDs) have been shown to reduce disease activity in relapsing-remitting multiple sclerosis (RRMS) patients, especially in terms of annualised relapse rate (ARR) and magnetic resonance imaging (MRI) findings.

According to Prof. Brassat, currently available DMDs are unable to effectively stop the course of the condition, but early treatment can delay disability progression in MS patients. The patient response to DMDs is, however, variable with some patients achieving significantly higher response levels to DMD therapy than others. Therefore, reliable response predictors that allow an optimized and individualized treatment are needed.

Several studies, including genome-wide association studies (GWAS), have tried to identify genetic variations responsible for the heterogeneous patient response to DMDs like interferon (IFN)-beta and Copaxone in RRMS. Based on these studies, genes like GPC5 (a glutamate receptor), ADAR, and SLC9A9 have been suggested to play a role in the response to IFN-beta treatment.

“A SLC9A9 variant influences disease activity in treated patients. This gene variant was [found to be] important to predict who would have more relapses.” explained Prof. Brassat during his presentation.

Based on these reports, Teva is now conducting a large-scale pharmacogenomics study in RRMS patients treated with Copaxone. The company developed an 11-single nucleotide polymorphism (SNP) signature for the Copaxone response in order to be able to predict high and low responders among RRMS patients who have not initiated treatment with this drug. The predictive value of the Teva’s multi-SNP signature is currently being assessed in several independent cohorts of patients.

Prof. Brassat said he believed the pharmacogenomics field “will rapidly evolve due to the knowledge surge in genetic techniques” and that it “is a tool for defining extreme responders/patients at risk of severe adverse events”, helping in the choice of the most adequate drugs and treatments for disease management. He concluded that “given the heterogeneity of MS, there is no best treatment strategy available today. However, pharmacogenomics is a promising approach to navigate personalized medicine from bench to bedside due to the robustness and high translational potential to clinical practice”.

Source: Multiple Sclerosis News Today © BioNews Services, LLC 2015 (12/10/15)

Long-term efficacy of Gilenya reinforced by new analysis (12/10/15)
Novartis has announced a new analysis from the phase III FREEDOMS and FREEDOMS II trials reinforcing the long-term efficacy profile of Gilenya. The analysis evaluated the proportion of Gilenya patients with relapsing-remitting multiple sclerosis (RRMS) achieving 'no evidence of disease activity' (NEDA-4) every year over seven years.

NEDA-4 is achieved when a patient has no relapses, MRI lesions, MS-related brain shrinkage and disability progression. These data were presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.

This follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with RRMS. The data showed that in the first year, 27.1 per cent of patients on Gilenya achieved NEDA-4 compared to 9.1 per cent on placebo. Switching from placebo to Gilenya after year two doubled the proportion of patients achieving NEDA-4 (12.7 per cent to 27.4 per cent) in year three. Of those patients on continuous Gilenya treatment, 31.2 per cent to 44.8 per cent had NEDA-4-status in each of the years three to seven.

Long-term efficacy of Gilenya® reinforced by new 'no evidence of disease activity' (NEDA-4) analysis in MS patients over seven years

Novartis announced today a new analysis from the phase III FREEDOMS and FREEDOMS II trials reinforcing the long-term efficacy profile of Gilenya® (fingolimod). The analysis evaluated the proportion of Gilenya patients with relapsing multiple sclerosis (RMS) achieving 'no evidence of disease activity' (NEDA-4) every year over seven years[1]. NEDA-4 is achieved when a patient has no relapses, MRI lesions, MS-related brain shrinkage and disability progression. These data were presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.

This follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with RMS. The data showed that in the first year, 27.1% of patients on Gilenya achieved NEDA-4 compared to 9.1% on placebo. Switching from placebo to Gilenya after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous Gilenya treatment, 31.2% to 44.8% had NEDA-4-status in each of the years three to seven.

"This data is important in showing the long-term efficacy of Gilenya, and the importance of early treatment to help improve long-term outcomes for patients," said Vas Narasimhan, Novartis Global Head of Development.

"Better understanding of the course of a person's MS through assessment of NEDA-4 can help physicians identify the optimal, effective treatment approach as early as possible for their patients."

Source: Novartis Global © 2015 Novartis AG (09/10/15)

Suicide rate ‘almost double in MS patients’ (09/10/15)
Patients with multiple sclerosis are more than twice as likely as the general population to attempt suicide and almost twice as likely to actually complete suicide, a new study has claimed.

The study also had some interesting results with regard to education. Although highly educated patients with MS are less likely to attempt suicide than their counterparts without MS, this is not the case when it comes to completed suicide.

Patients with MS should be screened for psychiatric disorders, said lead researcher Philip Brenner, MD, PhD student, Department of Neuroscience, and resident psychiatrist, Karolinska University Hospital, Stockholm, Sweden.

"Since neurologists are primarily the ones treating MS patients, they should be aware of the increased suicide risk and the risk for suicide attempts among these patients," Dr Brenner told Medscape Medical News.

"It's very important to include screening measures for mental health in clinical practice."

As well as depression, which is probably the most important risk mediator for suicide prevention in MS, physicians might also watch for personality changes, for example, having less impulse control and increased substance abuse, he said.

He presented their results at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015.

The study included 29,617 patients with MS from the combined Swedish National Patient Register and Swedish MS Register. It also included 10 controls without MS for each case from the Swedish general population who were matched with the MS group for year of birth, sex, and county of residence.

Researchers used diagnostic codes for intentional self-poisoning or injury to identify attempted suicides, and the Swedish Cause of Death register to identify completed suicides. They excluded deaths in which the intent was unclear.

There were 423 attempted suicides among patients with MS during the follow-up period (1968 to 2012) for an incident rate (IR) of 116.5 per 100,000 person-years. In patients without MS, the IR was 50.8. The adjusted hazard ratio (HR) was 2.18.

Women were at 30 per cent higher risk for attempted suicide compared with men in both the MS and control groups.

From census data, the researchers determined categories of education level achieved by study participants. As expected, they found that the risk for attempted suicide was lowest among patients with MS and controls with the highest level of education (14 or more years).

During the follow-up period, 114 patients with MS who committed suicide, for an IR of 30.31 per 100,000 person-years. This compared to an IR in patients without MS of 16.8. The adjusted HR for completed suicide was 1.87.

Dr Brenner said patients with MS who committed suicide chose means that were less violent than those without MS — for example, taking an overdose of pills rather than other means. "We don't have a good explanation for this," he said.

The risk for completed suicide was not lower among highly educated patients with MS, although it was for educated controls. There's evidence that an adverse event in adulthood (such as an MS diagnosis) can counteract the protective effect of socioeconomic status in terms of depression rates. "Maybe that's also true for MS," said Dr Brenner.

"With this difference in mind, it's possible that the effect of education is different in the two groups," he said. "But this needs to be investigated further."

Source: Medscape Medical News © 2015 WebMD, LLC (09/10/15)

Pregnancy ‘not neuroprotective for women with MS who stop taking Tysabri’ (09/10/15)
The possible protective effect of pregnancy on multiple sclerosis activity in women does not extend to patients who stop taking Tysabri after conceiving, researchers revealed at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Of 59 women treated with Tysabri who discontinued the drug during pregnancy, 12 experienced relapses and seven others had two or more relapses for a relapse rate of 32.2 per cent, reported Emilio Portaccio, MD, a neurologist at the University of Florence.

“In our sample, following Tysabri suspension, pregnancy did not prevent disease reactivation,” he said in his oral presentation.

In addition, he reported the rate of spontaneous abortions among women who had been taking Tysabri was greater than it was for a similar cohort of women taking interferon therapies or who had no treatment with disease-modifying drugs.

The study included MS patients who had been diagnosed and treated with Tysabri at one of 21 Italian centres from 2010 to 2013. The women were followed for at least 12 months after delivery. The researchers compared outcomes for women on Tysabri who had discontinued therapy — either to have a baby or who became pregnant — with women with MS who had been treated with interferon agents and women who were not exposed to disease-modifying drugs, or who had discontinued interferon therapy at least four weeks before conception. They were also compared to the general Italian population.

Of the 75 women who stopped their Tysabri therapy, there were 59 pregnancies, 45 live births, and 11 spontaneous abortions at a rate of 18.7 percent. The researchers compared outcomes for that group with those of 398 women taking interferon-based treatments, in which there were 88 pregnancies, 75 live births, and seven spontaneous abortions at a rate of 8 percent, a statistically significant difference. Of the women not exposed to disease-modifying drugs, there were 295 live births, 20 spontaneous abortions at a rate of 6.6 per cent, one stillbirth, and two extra-uterine pregnancies.

Dr. Portaccio said that all of the groups fell within the general population in Italy, however, where the spontaneous abortion rate declined between 4.4 per cent and 21.6 per cent.

In the Tysabri-exposed pregnancies, there was a slight reduction in the baby birth rate, but that was comparable to what was seen in the women whose babies were exposed to interferon in the womb. “We observed no major birth defects and no difference between the groups in the rate of birth defects,” he said.

Commenting on the study, the session co-moderator Charlotte Teunissen, PhD, an associate professor of medicine and head of neurochemistry at the VU University Medical Center of Amsterdam, told the Neurology Today Conference Reporter that the study suggests that “patients and doctors [should] wait as long as possible before taking women off natalizumab when they become pregnant.”

She added: “Pregnancy normally has a very positive effect on multiple sclerosis activity, but this study shows that this effect is too small to overcome the very strong rebound observed with discontinuation of Tysabri.

“Doctors should be encouraged to hold off suspending Tysabri unless they fear continuing would harm the fetus,” Dr. Teunissen said. “This would obviously be up to the discretion of the treating physician and the patient. The greatest risk would be spontaneous abortion, although it was within the normal range in this study. There did not seem to be any greater risk of birth defects or even low birthweight.”

Source: Neurology Today Copyright © 2015 American Academy of Neurology (09/10/15)

Tysabri every eight weeks may cut PML risk (09/10/15)
Preliminary findings from an ongoing study of multiple sclerosis patients suggest the dosing interval for Tysabri can be as much as doubled from the label-recommended standard without sacrificing efficacy, and with potentially less risk of progressive multifocal leukoencephalopathy (PML) -- even among patients with more than average PML risk, researchers claim.

Among some 2,000 patients -- about half of whom were receiving Tysabri at intervals ranging from 31 to 61 days, versus the standard 28-day cycle in the other half -- measures of efficacy were the same or better in those on extended-interval dosing, said Lana Zhovtis-Ryerson, MD, of NYU Langone Medical Centre in New York City, who presented the findings at a platform session during the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

Furthermore, no cases of PML were seen in the extended-dosing patients, compared with four among those taking Tysabri on the conventional four-week schedule, she said.

She cautioned, however, that the findings on PML risk are not yet definitive because there are not yet enough data in the ongoing study for the differences to reach statistical significance.

But at this point, it does appear that the extended-dosing strategy does maintain efficacy in relapsing-remitting MS patients.

Earlier this year, when Zhovtis-Ryerson and colleagues reported initial results from the study, there were two cases of PML in the standard-dose group versus none receiving extended dosing, and relapse rates and MRI activity levels were similar. At that time, and again here, she said 1,248 patient-years of exposure would be needed to pronounce a significant advantage for one dosing strategy.

Currently, she said the standard-dose group had 1,052 patient-years among JC virus-positive participants and 1,090 patient-years in the extended-dosing group.

However, accrual of patient-years of exposure is proceeding slowly, she told MedPage Today, and the research team expects it will be another 18 months before both groups reach the 1,248 mark.

Label instructions for Tysabri dosing call for the drug to be given every four weeks. But researchers have wanted to determine whether the same degree of clinical efficacy, in reducing risk of relapses and MRI lesion activity, can be maintained with longer intervals -- the point being to reduce the overall drug exposure and with it, presumably, the risk of developing PML.

Rates of PML have been found to increase with years of Tysabri exposure, but it remains unknown whether reducing the exposure in terms of milligrams per year will also cut the PML risk.

PML has been the biggest barrier to use of Tysabri, which otherwise is a highly effective and relatively safe agent for relapsing-remitting MS. Among patients positive for JC virus (the actual causative agent) who remain on Tysabri for more than two years at standard dosing, between 0.5 and one per cent will develop PML, depending on prior exposure to immunosuppressants. Roughly 20 per cent of PML cases are fatal and many survivors have permanent disabilities.

The current study's design involves regular chart reviews, conducted on a prospective basis but without randomized treatment assignments, of patients receiving natalizumab on a variety of dosing schedules chosen by their treating physicians on an individualized basis. Zhovtis-Ryerson and colleagues have stratified patients into the following groups:

Standard dosing (every four weeks)
Extended dosing (every 31 to 61 days)

That no patients in the latter group developed PML, versus four with standard dosing, is all the more impressive because the recognized risk factors for PML were more common in those receiving the extended dosing -- as might be expected since clinicians may be inclined to recommend less frequent natalizumab dosing for patients deemed to have high PML risk.

Zhovtis-Ryerson emphasized that data from the current study may never be fully adequate to justify extended dosing as a routine strategy. She urged that a prospective, randomised non-inferiority trial be conducted.

Source: MedPage Today © 2015 MedPage Today, LLC (09/10/15)

Studies confirm Sativex helps in MS spasticity (09/10/15)
Multiple sclerosis patients taking the cannabis-based spray Sativex to relieve spasticity are getting approximately the same degree of benefit expected from the product's formal trials, according to interim results from two observational studies from Italy reported here.

Modest but statistically significant improvement in spasticity scores (10-point Numerical Rating Scale, NRS) has been seen among 322 patients who added Sativex to standard anti-spasticity drugs and/or physical therapy, according to a group led by Maria Trojano, MD, of the University of Bari, whose ongoing study is called MOVE 2 and who reported data from the first three months after enrollment.

A separate study dubbed SA.FE led by Francesco Patti, MD, of the University of Catania, has also yielded similar results during the first few months of therapy, with about 40% of 547 patients showing at least a 30% improvement in NRS scores at 6 months.

Both studies were reported at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

Sativex is a 50:50 mixture of the cannabis components THC and cannabidiol, sprayed into the mouth daily to help control spasticity symptoms. It was approved in Italy for marketing in mid-2013 on the basis of randomized trials showing a benefit over placebo, primarily in patient-reported measures. Those findings led the American Academy of Neurology last year to declare Sativex appeared effective in patients' subjective judgment (though the group questioned the product's efficacy according to objective measures).

Because clinical trials usually enroll carefully selected patients, with many exclusions and close monitoring of those enrolled, there are often questions about the relevance of these results in real-world patients. Hence, the MOVE 2 and SA.FE studies were started to examine how Sativex is working in routine practice environments.

MOVE 2 actually began in Germany and was subsequently extended to other European countries following Sativex's approval there, Trojano and colleagues noted. In the Italian version, outcomes according to both the patient-reported NRS score and the objective Ashworth scale (measuring resistance to muscle stretching) are being collected.

The current report included results from the first 322 patients to complete three scheduled clinic visits after starting Sativex. The initial visit was at enrolment, the second occurred one month later, and the third took place 2 months after that. Patients were asked about concomitant treatments and adverse effects. Data on quality of life, satisfaction with treatment, and other issues are being collected as well, but were not reported here.

More than two-thirds of MOVE 2 participants said they were also taking baclofen, and smatterings of others reported using benzodiazepines, pregabalin, gabapentin, and/or other agents. About half were taking physical therapy as well.

At the one-month visit, 83 per cent of patients had NRS scores that were at least 20 per cent better than at the baseline visit. At the three-month evaluation, with 203 patients having sufficient data, about one-quarter showed at least 30 per cent improvement from baseline in NRS score, and most of the others continued to use Sativex despite showing less than 30 per cent improvement.

By the third visit, 22 per cent had discontinued the product. About 40 per cent of those were for lack of efficacy and an equal proportion cited adverse effects; the remainder had become pregnant or had other reasons to stop the drug.

Mean dose at the one-month visit was 6.1 sprays/day (SD 2.5); at the third visit it was 5.1 sprays/day (SD 2.6).

On the objective Ashworth scale, Sativex also appeared effective: from a baseline mean of 2.6 on the 4-point scale, the mean declined to 2.2 at the second visit (P<0.0001) and stood at 2.3 at the third visit (P<0.0001 versus baseline), with 220 and 149 patients evaluated at the respective visits.

More than 80 per cent of patients reported no adverse effects; of those that did, the chief complaints were dizziness, confusion, nausea, and somnolence.

Trojano and colleagues indicated that they expect final results next year.

For the SA.FE study, Patti and colleagues indicated that their data were not much more mature, with only about one-third of the 1,534 patients currently enrolled having reached the six-month mark. Also, their report only had NRS data.

However, those results clearly support a benefit for Sativex during this time frame. In the first month, there was an average 22.6% decrease in NRS score among all participants, with 62% of patients obtaining at least 20% improvement.

About 600 patients have discontinued thus far -- as in MOVE 2, the most common reasons were lack of efficacy and adverse effects.

Source: MedPage Today © 2015 MedPage Today, LLC (09/10/15)

DMF ‘reduces disease activity long-term in MS’ (09/10/15)
Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) is effective at lowering disease activity long-term in patients with relapsing-remitting multiple sclerosis (RRMS), according to Eva Havrdova, MD, of Charles University of Prague.

The findings were being presented in a poster session at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.

A duo of studies, DEFINE and CONFIRM, previously found patients taking DMF were nearly two times as likely to show no disease activity (NEDA). The findings proved to hold true for five years and the research moved onto an eight-year extension study, ENDORSE. Long-term results, however, were lacking.

Havrdova and team randomised patients to receive either DMF 240 mg twice per day, three times per day, a placebo, or glatiramer acetate. Overall NEDA was defined as patients with no relapses, no 12-week Expanded Disability Status Scale (EDSS)-confirmed progression, no gadolinium-enhanced lesions, and no new or enlarged T2 lesions.

After two years, 1,118 out of 1,736 ENDORSE patients had clinical NEDA and only 618 did not. Magnetic resonance imaging (MRI) results showed that out of the 799 patients who had data on all four components of NEDA, 171 had overall NEDA and 628 did not.

“At Year three in ENDORSE, the annualised relapse rate was significantly lower in patients with clinical and overall NEDA vs those without,” the authors confirmed.

“Throughout the three years in ENDORSE, clinical and overall NEDA patients maintained significantly lower EDSS scores than those without.”

The outcomes suggest that compared to a placebo, DMF significantly reduces disease activity.

Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC (09/10/15)

Online CBT reduces fatigue in MS, new data shows (09/10/15)
A fully-automated and interactive online fatigue management program for patients with multiple sclerosis is comparable to in-person cognitive behavioural therapy (CBT) for the reduction of fatigue, according to data presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.

In previous trials, face-to-face CBT or exercise programs were shown to be efficacious in reducing fatigue in patients with MS. For this study, Jana Poettgen, a cognitive psychologist at the University Medical Centre Hamburg Eppendorf in Hamburg, Germany, and colleagues developed the ELEVIDA online fatigue management program based on a manualised face-to-face CBT intervention.

The researchers sought to see how the intervention primarily affected fatigue as measured by the Chalder Fatigue Scale, as well as cognition, quality of life, anxiety, mood, and self-reported neuropsychological function in patients with MS.

The researchers recruited 275 patients from the German Multiple Sclerosis Society; 139 were randomised to ELEVIDA and 136 to the waitlist control group. At baseline, both groups were comparable in age, sex, education, disease duration, and disease course. Overall, 224 of the 275 participants completed an assessment at the three-month follow-up. The ELEVIDA program significantly reduced fatigue, and the ELEVIDA group also reported significant improvements in anxiety and subjective cognitive impairment, however no significant treatment effects were seen for depression or coping.

Overall, the online ELEVIDA program showed efficacy for the reduction of fatigue in MS, and may be a more cost-effective treatment option. The researchers are now studying whether the effects of the program can be maintained over longer follow-up periods.

Reference: Poettgen J et al. Abstract 135. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc.(09/10/15)

Roche drug shows promise for less common form of MS (09/10/15)
Swiss drugmaker Roche has said its experimental treatment for multiple sclerosis performed better in a late-stage clinical trial than a commonly used therapy for the most prevalent form of the condition.

The drug, ocrelizumab, also showed a benefit in primary-progressive MS, or PPMS, giving it the potential to be the first medicine on the market for those patients.

"For decades, we've tried different medicines to treat the primary progressive forms of the disease and nothing has worked," said Dan O'Day, Roche chief operating officer of Pharmaceuticals.

"Ocrelizumab is the first medicine to show an effect in significantly reducing the progression for patients with progressing multiple sclerosis. We're very excited about the benefit that could bring to patients."

The results were from three studies being presented at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Barcelona.

Roche's ocrelizumab is given by infusion once every six months, significantly less frequently than most other MS medicines. The company compared its drug with Merck KGaA's Rebif, an older therapy administered by shot three times a week.

In two studies in relapsing-remitting MS, ocrelizumab reduced patients' risk of flare-ups by almost half over two years compared with Rebif, Roche said in a statement. It also delayed progression of disability by about 40 per cent and reduced brain lesions by about 80 per cent, Roche said.

The most common side effect was infusion-related reactions.

In PPMS, the less common form, Roche compared ocrelizumab with a placebo given the lack of approved therapies. There the medicine also met study goals, reducing the risk of disability progression over 12 weeks by 24 per cent.

The medicine is Roche's first in multiple sclerosis.

Source: CNBC © 2015 CNBC LLC (09/10/15)

Aubagio ‘slows brain atrophy in RRMS patients’ (09/10/15)
Genzyme has announced results from magnetic resonance imaging (MRI) analysis of participants in the Phase III TEMSO clinical trial showing Aubagio was able to slow the loss of brain volume (or atrophy) versus a placebo over two years in patients with relapsing-remitting multiple sclerosis (RRMS).

Brain volume loss (BVL) is widespread in multiple sclerosis (MS), and occurs throughout the disease course at a rate considerably greater than in the general population. In MS, brain volume correlates with and predicts future disability, making BVL a relevant measure of diffuse central nervous system (CNS) damage leading to clinical disease progression, as well as serving as a useful outcome in evaluating MS therapies.

TEMSO MRI data was analysed with SIENA (structural image evaluation using normalization of atrophy). SIENA is a fully automated method for finding temporal brain changes, taking as input two MRI images at different points in time, and giving as output a “change” image, along with a global estimate of percentage brain volume change.

Change in brain volume from baseline was measured in RMS patients who received treatment with Aubagio (14 mg or 7 mg) or a placebo. Results from studies with MS patients treated with Aubagio showed that the incidence of serious adverse events was analogous among patients treated with the drug and those treated with the placebo.

The analysis results will be presented this week, on October 10, at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which is taking place in Barcelona, Spain.

“These results showing the reduction in brain atrophy over two years add to the growing body of data for Aubagio,” said Bill Sibold, Head of Genzyme’s Multiple Sclerosis business. “We remain committed to furthering the understanding of Aubagio and the potential benefits it could deliver to relapsing MS patients.”

Aubagio, a pyrimidine synthesis inhibitor, is an oral compound that inhibits the function of specific immune cells that have been implicated in MS. It is related to leflunomide, a drug used to treat rheumatoid arthritis. Aubagio can inhibit a key enzyme required by white blood cells (lymphocytes) – which in turn reduces the proliferation of T and B immune cells that are active in MS, and also inhibits the production of immune messenger chemicals by T cells.

Aubagio was approved by the U.S. Food and Drug Administration (FDA) in September 2012 for patients with relapsing forms of MS.

“Control or prevention of brain atrophy is an important target for MS treatment,” said Prof. Dr. Ludwig Kappos, Neurology Chair, University Hospital Basel, Switzerland. “This data helps provide further insight into the potential effects in people with RMS.”

Source: Multiple Sclerosis News Today © BioNews Services, LLC 2015 (09/10/15)

Early Gilenya generics spell trouble for rival MS drugs (08/10/15)
Last week, the U.S. Patent Trial and Appeal Board took a long-term Gilenya patent out of commission, putting the Novartis multiple sclerosis drug in line for early generic competition.

While not good news for the Swiss drugmaker, it's not good for rival pharma companies, either as they will also have to contend with copycat versions of Gilenya, the first oral treatment for MS.

"Without novel IP, Gilenya will go generic in 2019 with multiple entrants," Bernstein analyst Ronny Gal said.

Generic Gilenya would join knockoff versions of Teva's MS treatment Copaxone, and together, the two would put pressure on the rest of the treatments for the condition. Though Copaxone is an injectable, it's a mainstay of MS treatment, even in the face of competition from pills like Biogen's Tecfidera and Sanofi's Aubagio, in addition to Gilenya.

With both Gilenya and Copaxone copies available, those rival meds will be in trouble, Gal said.

"By 2019, with both Copaxone and Gilenya generics, I suspect the MS will reasonably lose pricing power and the generics will be used first line," the analyst told FiercePharma.

Source: Fierce Pharma © 2015 FierceMarkets (08/10/15)

New MS drug ‘yields mixed results’ (08/10/15)
Multiple sclerosis patients taking a new drug experienced fewer relapse rates but more side effects than patients receiving a standard MS therapy, new research indicates.

In a trial comparing two sets of more than 900 patients with relapsing-remitting multiple sclerosis, scientists found that those taking the drug daclizumab HYP had a 45 per cent lower relapse rate than those taking interferon beta-1a.

But patients on the new drug, which has not yet been approved by the U.S. Food and Drug Administration, saw more side effects. Also, they did not experience significantly slower disease progression than those in the interferon beta-1a group over the first several months.

"This is one more drug for multiple sclerosis, which is of course very welcome, but it's just one in addition to the 11 or 12 drugs we already have," said Dr. Eugene Lai, a neurologist at Houston Methodist Hospital in Houston, who was not involved in the research.

"It does reduce the relapse rate, but it probably doesn't get to the real core of the MS process, and we still don't understand exactly how relapse rate and progression are related," Lai added. "It's still not the definitive treatment for MS yet that can stop it."

The study was published in the New England Journal of Medicine.

In the new study, led by scientists at University Hospital Basel in Switzerland, more than 1,800 patients with relapsing-remitting MS were randomly assigned to receive either daclizumab HYP or interferon beta-1a over a period averaging about two years.

Daclizumab is a so-called monoclonal antibody drug and is thought to work by binding to receptors on immune system cells linked to multiple sclerosis and other autoimmune disorders. Interferon beta-1a is a synthetic version of a natural substance produced in the body that fights infections and other threats.

While daclizumab recipients experienced much lower relapse rates than those on interferon beta-1a, disability progression 12 weeks after the study's start was similar in both groups - 16 per cent with daclizumab and 20 per cent with interferon beta-1a.

But side effects, including serious infections and skin problems such as rash or eczema, were far more common among daclizumab recipients.

Johns Hopkins Hospital in Baltimore was one of the 244 study sites in 28 countries participating in the trial. Dr. Scott Newsome, director of neurology outpatient services at Hopkins, noted that daclizumab might be an easier regimen for MS patients because it's injected under the skin only once every four weeks. Interferon beta-1a requires a weekly infusion.

Another benefit, Newsome said, is that disease progression seemed to be slightly slower at the six-month mark and beyond in daclizumab patients.

"In my mind, that's the outcome measure to look at," he said. "MS is a marathon, not a 50-yard dash. As a group, we need to have better outcome measures in clinical trials that tell us long-term where a patient will be."

Lai and Newsome agreed that FDA approval for daclizumab seems likely, at which point a more complete idea of side effects will be available once the drug hits the market.

Newsome, also an assistant professor of neurology at Hopkins, said he wasn't sure how much daclizumab would cost if it becomes widely available, but it's likely its price would be far higher than for interferon beta-1a, which has been used for many years to treat MS.

"I think it's fantastic that we have a number of therapies to treat MS patients, because certainly throughout the years we're noticing an improvement in patients' overall quality of life and decreased disability over time," he said. "But it's becoming more complicated in terms of which medications we choose first or second, and some of what we decide is not driven by the doctor; often it's driven by the patient and insurer."

If daclizumab is FDA approved for use, Lai and Newsome said physicians should be vigilant for side effects.

"I myself will probably wait and let it be on the market for a while to make sure it's safe before I use it," Lai said. "We're encouraged to have so many effective medications for MS, but it's also kind of confusing to weigh the benefits versus the side effects and risks. It's important for patients to go to a doctor with more expertise in the treatment of MS to get the most benefit and select the right medication for them."

Source: HealthDay Copyright © 2015 HealthDay (08/10/15)

MS may be influenced by race and vitamin D levels 08/10/15)
Race and vitamin D levels may play a crucial role in the risk of multiple sclerosis (MS), according to Annette M. Langer-Gould, MD, PhD, of Kaiser Permanente in Pasadena, California.

Previous research has linked lower vitamin D levels with an increased risk of MS – but only in Caucasians. Langer-Gould and her team set out to see if the same could be said about African Americans and Hispanics. They looked at patients with newly diagnosed MS or clinically isolated syndrome (CIS), the precursor, between 2011 and 2014.

The researchers gathered data from 929 individuals (457 with MS/CIS and 472 healthy controls) through interviews, blood tests, and complete electronic health records. Patients and controls were matched for age, sex, and race/ethnicity:
Caucasian: 203 patients, 205 controls
African American: 108 patients, 116 controls
Hispanic: 146 patients, 151 controls

Overall, Caucasians had the highest levels of 25-hydroxyvitamin D (average of 70nmol/L) followed by Hispanics (55nmol/L) and African Americans (47nmol/L). Higher vitamin D levels were associated with lower risk of MS/CIS in Caucasians, especially those with levels over 75nmol/L. However, the findings did not show a correlation between vitamin D levels and MS/CIS risk in African Americans or Hispanics.

“A non-causal association cannot be excluded as vitamin D is a better surrogate measure of sunlight exposure in light than dark-skinned individuals,” the authors explained. “Another possible explanation is complex interactions between vitamin D and genotype as several genes that increase vitamin D bioavailability are more common in blacks.”

Prescribing vitamin D to prevent MS is premature, the team advises. The research reaffirms the importance of considering race in vitamin D studies.

Source: Specialty Pharmacy Times Copyright Specialty Pharmacy Times 2006-2015 Intellisphere, LLC (08/10/15)

Treatment effects maintained over five years in Lemtrada patients (08/10/15)
Genzyme, has announced new five-year investigational data from the extension study of Lemtrada for patients with relapsing remitting multiple sclerosis (RRMS).

In RRMS patients treated with Lemtrada in the Phase III studies, the effects observed in the two-year trials were maintained through three additional years in the extension study.

The low annualized relapse rates observed in patients who received Lemtrada in CARE-MS I and CARE-MS II were maintained from year three to year five.

Through year five, 80 per cent and 76 per cent of patients who received Lemtrada in CARE-MS I and CARE-MS II, respectively, did not experience worsening of disability progression confirmed over six months as measured by the Expanded Disability Status Scale (EDSS).

Through year five, 33 per cent and 43 per cent of patients who had some disability before receiving Lemtrada in CARE-MS I and CARE-MS II, respectively, had improvement in EDSS score confirmed over at least six months as compared with pre-treatment baseline.

Through year five, patients who received Lemtrada in CARE-MS I and II experienced a slowing of brain atrophy as measured by brain parenchymal fraction on magnetic resonance imaging (MRI). In years three, four and five, the median yearly brain volume loss was -0.20 percent or less, which was lower than what was observed during the two-year pivotal studies.

In each of years three, four and five, most patients had no evidence of MRI disease activity (70 – 72 per cent, CARE-MS I; 68 – 70 per cent, CARE-MS II.)

Through year five, the incidence of most adverse events during the extension study was comparable or reduced compared with the pivotal studies. The frequency of thyroid adverse events was highest in year three and declined thereafter.

More than 90 percent of the patients who were treated with Lemtrada in the CARE-MS Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions.

“This data illustrates that most Lemtrada patients experienced sustained effects of treatment, despite the absence of additional treatment courses,” said Professor Eva Havrdová, MD, PhD, MS Center, Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic.

"It is encouraging to see consistent effects maintained across multiple meaningful outcomes through five years.”

Source: Business Wire ©2015 Business Wire (08/10/15)

Spinal cord grey matter atrophy ‘has greatest clinical impact in MS’ (08/10/15)
Researchers say they have found a strong relationship between spinal cord grey matter atrophy with disability and multiple sclerosis, which they said was much stronger than the relationship for any known cortical grey or white matter metric.

The results were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.

“This study was driven by the clinical observation that MS progression manifests as a progressive myelopathy in the majority of patients,” Regina Schlaeger, MD, study investigator from the department of neurology at the University of California, San Francisco, told Neurology Advisor.

“Our finding that the spinal cord grey matter was, among other conventional MRI metrics, most relevant in explaining disability was rather unexpected.”

For the study, Dr. Schlaeger and colleagues enrolled 142 patients with MS and 20 controls and scanned them with 3T MRI. The researchers acquired axial 2D phase sensitive inversion recovery (PSIR) images at disc levels C2/3, C3/4, T8/9 and T9/10. They segmented total cord areas (TCA) semi-automatically and spinal cord grey matter manually, and determined between group differences in areas with age and sex as covariates.

Compared with controls, cervical and thoracic spinal cord relapsing MS patients had smaller grey matter areas, although there were no significant differences in either spinal cord white matter area or TCA. Smaller grey matter areas were reported in progressive MS patients vs. relapsing MS patients, as were smaller TCAs.

Multivariable model results demonstrated the strongest correlation between cervical spinal cord grey matter area and Expanded Disability Status Scale (EDSS), followed by thoracic spinal cord grey matter area and brain grey matter volume.

In addition, researchers reported the following areas under the ROC curve for the prediction of a progressive course based on logistic models:

“Traditionally, spinal cord atrophy is thought to be mostly driven by axonal (white matter) loss. We found a preferential reduction in spinal cord grey matter in progressive patients and, moreover, a subtle but selective grey matter atrophy in relapsing patients,” Dr. Schlaeger said. “The cervical spinal cord grey matter area was strongly associated with disability (EDSS) and progressive phenotype, indicating that spinal cord grey matter atrophy is indeed clinically relevant. However, the validity of spinal cord grey matter assessments as a biomarker of progression needs to be further determined in longitudinal studies.”

Reference: Schlaeger R et al. Abstract 208. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (08/10/15)

“Novel approaches” needed for MS, claims doctor (08/10/15)
In patients with primary progressive multiple sclerosis (PPMS), Gilenya resulted in similar mean percent brain volume change (PBVC) and per cent change in spinal cord area (PCSCA) vs. placebo, according to data from the INFORMS study.

“Anti-inflammatory strategies currently successfully applied in RRMS cannot be automatically translated into the PPMS population,” Özgür Yaldizli, MD, study investigator and neurologist from the UCL Institute of Neurology, Queen Square Multiple Sclerosis Centre, London, told Neurology Advisor.

“We need novel approaches to treat people with PPMS.”

Yaldizli presented the results at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.

The catalyst for the analysis, Dr. Yaldizli said, was that in the past decade, studies have consistently shown that brain and spinal cord atrophy are more closely related to clinical disease progression in MS than magnetic resonance imaging (MRI) markers of inflammation. This led Dr. Yaldizli and colleagues to enroll 823 patients and follow them for three years. Patients were included if they had a clinical diagnosis of PPMS; disease duration of two to 10 years; and objective evidence of disability progression in the previous two years.

“Although the PPMS patients included in the INFORMS trial had a relatively low level of MRI-detected inflammation, the effect of Gilenya on MRI-markers of inflammation was consistent with that observed in RRMS patients,” Dr. Yaldizli said. “However, disappointingly, in INFORMS, there was neither a significant treatment effect on disease progression nor on brain or cervical spinal cord atrophy.”

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (08/10/15)

Good cholesterol helps prevent brain lesion formation in MS (08/10/15)
A number of studies have previously suggested a negative effect of high cholesterol levels on the development of brain lesions in patients with multiple sclerosis, however, little is known about the effect of HDL (high-density lipoprotein) cholesterol, or “good” cholesterol, on MS.

Now, a team of scientists from the University of Buffalo has found that good cholesterol has protective properties for the blood-brain barrier. The study, Protective Associations Of HDL With Blood Brain Barrier Injury In Multiple Sclerosis Patients, has been published in the Journal Of Lipid Research.

“This finding is especially important because we found this protective effect very early in the disease,” said the study’s lead author Murali Ramanathan, PhD, a professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences, and professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo.

To better understand the impact of HDL on MS, the team followed a group of patients for four years following their first experience of an attack of MS symptoms. The results offer a number of implications, not only in treatment discovery and development, but also in the drafting of future guidelines for MS prevention and management.

“This is the first time HDL cholesterol has been found to have such a clear benefit against the breakdown of the blood-brain barrier in MS patients,” said Dr Ramanathan.

“The breakdown of the BBB [blood-brain barrier] is the first step in the formation of brain lesions because it allows immune cells to enter the brain, form long-lasting lesions and mediate tissue injury.

“Cholesterol profiles can be affected by several factors including genetics, diet, smoking and physical activity. A better understanding of this key class of modifiable factors could be leveraged both as clinical advice to MS patients seeking to reduce the risk of progression and as the basis of guidance to healthy individuals with genetic and other known risk factors for MS.”

Source: Multiple Sclerosis News Today © 2015 BioNews Services, LLC (08/10/15)

Team investigate exercise benefits (07/10/15)
A study has concluded that high-intensity exercise can improve muscles and stamina in people living with multiple sclerosis.

The study, High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial by Inez Wens, Ulrik Dalgas, Frank Vandenabeele, Lotte Grevendonk, Kenneth Verboven, Dominique Hansen, Bert O. Eijnde, looked at three groups of MS patients.

One group were the sedentary control, while the other two groups performed high-intensity exercise – either continuously or at intervals – over a 12 week period.

The study concluded that 12 weeks of high intensity cardiovascular exercise in combination with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity, with interval training seemingly superior to continuous training.

Source:: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133697 (0710/15)

Limited Fampyra funding approved in Ireland (06/10/15)
Ireland’s Health Service Executive has agreed to fund ‘on a limited basis’ the cost of a drug that helps people with multiple sclerosis to walk.

The announcement that Fampyra is to be reimbursed under the State-funded drugs schemes follows a lengthy campaign by patients who say the drug has greatly aided their mobility.

The HSE says it is in the final stages of putting in place the arrangement around a “responder-based” reimbursement programme for Fampyra.

The cost of the drug will be covered where a demonstration of clinical response, based on objective criteria agreed with clinical experts, is recorded, it says. This clinical response must be shown to persist based on objective measurement at six-monthly intervals.

Annual cost
In 2013, the National Centre for Pharmacoeconomics, which rules on the cost-effectiveness of new drugs, found Fampyra would cost nearly €7,000 per patient each year. It said the €20 million annual cost to the State over five years would take money from other areas.

The HSE then decided that it could not approve the reimbursement of Fampyra and claimed the manufacturer, Biogen Idec, had failed to demonstrate or provide any formal justification for the prices proposed. Biogen maintained it had offered significant price reductions in the talks.

Agreement has now been reached on a reimbursement arrangement.

Patients have been paying up to €500 a month for Fampyra from their own resources after Biogen started charging for the drug last year following a free trial period.

Multiple Sclerosis Ireland expressed delight with the progress on reimbursing Fampyra, which it said had a significant impact on patients’ ability to remain independent.

Source: http://www.irishtimes.com/news/health/hse-to-fund-on-limited-basis-cost-... (06/10/15)

New study removes cancer fear for potential MS drug (06/10/15)
Researchers from Queen Mary University of London (QMUL) are calling on the medical community to reconsider developing a known drug to treat people with relapsing-remitting MS after new evidence shows it does not increase the risk of cancer as previously thought.

The drug called Cladribine is already licensed and in use for people with leukemia. Previous studies, ran with patients at Barts Health NHS Trust in London, showed Cladribine to be highly effective in treating relapsing MS. One trial showed the drug reduced relapses by over 50 per cent, and nearly 50 per cent of people showed no signs of disease activity at all over two years. However, Cladribine was refused market authorisation on the suspicion it may cause cancer based on the interpretation of previous data.

A new study published in the journal Neurology: Neuroimmunology & Neuroinflammation compared the incidence of cancer where patients had been treated with Cladribine to other studies where they had been treated with other similar drugs that are currently licensed for MS.

The team from the Blizard Institute at QMUL compared data from the 11 pivotal trials that were used to support the licensing of seven different drugs to examine the cancer risk. They found there was no evidence for an increased risk of cancer in people with MS taking Cladribine.

Cladribine appears to be more effective, safer, easier to use and could potentially be cheaper than other current drugs used to treat MS.

“Our research shows that clinical academics and drug makers should continue to develop Cladribine for people with relapsing MS as the risk of developing cancer is no greater than for other types of current medication,” saidDr Klaus Schmierer, lead author and Reader in Clinical Neurology at QMUL and Consultant Neurologist at Barts Health NHS Trust.

He added: “As well as being easier and cheaper to administer, Cladribine benefits female patients who want to get pregnant. Other drugs used to treat relapsing MS need to be stopped during pregnancy and that can expose women to increased risk of MS disease activity. That’s not the case with Cladribine, which has a long lasting effect.”

It is estimated that over 120,000 people with MS live in the UK and it affects over two million patients globally. MS, which is a chronic, inflammatory condition of the central nervous system affects young adults and has a substantial impact on quality of their life, employment, and relationships.

Source: Queen Mary University of London, http://www.qmul.ac.uk/media/news/items/smd/164455.html (01/10/15)

Studies propose vaccination for PML (06/10/15)
Two research teams say they may have found an unexpected way to prevent or treat the common virus found in many healthy people which can cause a rare but potentially lethal brain disease, progressive multifocal leukoencephalopathy (PML), in those with altered or weakened immune systems.

There have also been reported cases of PML in people taking the MS therapy Gilenya.

One team came up with a vaccine that can boost overall immune response against the virus, a prophylactic tactic to prevent the raging brain infection (Ray et al., 2015). Another group reports that an antibody mix engineered from PML survivors may be a promising treatment for those who develop PML (Jelcic et al., 2015). The two papers were published together online in the journal Science Translational Medicine.

The new studies use too few patient samples and test cases to be definitive, but the results position both strategies for the next step of clinical testing, say the authors and others interviewed by MSDF. Independent of the potential therapeutic application, the findings also add fuel to a debate about the underlying mechanism of PML.

Concern about PML discourages people from choosing a highly effective treatment for RRMS and limits the time they can take it, said David Clifford, MD, a clinical neurologist at Washington University in St. Louis, Missouri, U.S., who was not involved in the new studies.

A 2005 report linked PML with monoclonal antibody therapy, specifically Tysabri, in two people with MS and one with Crohn’s disease. Tysabri blocks a receptor on T cells and prevents them from crossing from the blood into the brain. The drug was withdrawn from the market for one year.

PML prevention now relies mainly on prescreening high-risk patients and prescribing Tysabri for only a limited time, as well as close monitoring of people on any drug associated with PML.

Research in the small PML field has focused on the clear central role of T cells and the way the virus enters brain cells and replicates. Evidence from people with MS seemed to confirm that antibody-based immunity is nearly worthless in PML.

“You have to look at the right kind of antibodies,” said Diana Pastrana, PhD, a senior staff scientist in Buck’s lab and co-author of the paper, referring to specific neutralizing antibodies of JCV variants. They hypothesised that PML may arise from JCV mutants that evade the immune system.

To investigate that possibility, they started with cell assays. Serum from PML patients neutralised the wild-type JCV but not the JCV mutants commonly found in the brains of people with PML. In contrast, most of the serum from healthy people effectively neutralized all JCV types.

In mice, the researchers were able to close these antibody “blind spots” to the JCV mutants with a general vaccine made of virus like particles (VLP). The same VLP technology is used in the HPV vaccine and others on the market now.

The premise of the two papers rests on the assumption that the virus replicates and mutates, leading to PML. In the brains of people who have died from PML, scientists have found mutations in the JCV protein shell. Scientists still don’t know whether the surface mutations help JCV enter the brain and cause PML or whether the protein shell evolves when virus already in the brain goes wild in the absence of T cells.

The active and passive vaccination discoveries are protected by patents

Despite the interest of drug companies in preventing PML, the disease is so rare that they may hesitate to launch an expensive clinical trial, several experts told MSDF.

Source: Multiple Sclerosis Discovery Forum, http://www.msdiscovery.org/news/new_findings/22160-studies-propose-vacci..., by Carol Cruzan Morton (02/10/15)

Transcranial direct current stimulation promising for MS (06/10/15)
Transcranial direct current stimulation (tDCS) may help improve cognition and reduce mental fatigue in patients with multiple sclerosis (MS), results from a pilot study indicate. The findings were presented at theAmerican Neurological Association 2015 Annual Meeting in Chicago. Tracy D. Vannorsdall, PhD, of Johns Hopkins University School of Medicine, and colleagues conducted the small study in five patients with secondary progressive MS. The findings, while preliminary, show promise for tDCS as a future therapy for MS.

In a sham-controlled, single-blind crossover experiment, participants completed cognitive assessments (MAC-FIMS cognitive battery, Beck Depression Inventory II, and Fatigue Severity Scale) both before and after receiving 2 MA of anodal and sham tDCS to the left dorsolateral prefrontal cortex for 30 minutes, once a day for five consecutive days, while also performing cognitive rehabilitative tasks. There was a four-week washout period between therapies.

Those who received active stimulation showed a reduction in fatigue while an increase in fatigue was observed during sham stimulation. Results also showed a statistically significant improvement in verbal short-term memory, learning, and memory, and positive trends were also seen in working memory and other cognitive skills during active stimulation compared to sham stimulation. No change in depression scale ratings was observed for either therapy.

Overall, tDCS was found to be safe and well-tolerated, with results suggesting that it may ameliorate fatigue and cognitive dysfunction in MS.

Source: Neurology Advisor, http://www.neurologyadvisor.com/ana-2015-coverage/transcranial-direct-cu..., by Alicia Ciccone, 01/10/15

Transcranial Direct Current Stimulation promising for MS (06/10/15)

Smoking an MS Risk Factor Among MS Patients' Relatives (06/10/15)
Smoking is a risk factor for developing MS among first-degree relatives of confirmed MS patients, according to an ongoing study of more than 2,600 individuals.

The study, based on a model combining genetic and environmental risk factors to identify likelihood of developing MS, found in 1,696 first-degree relatives of MS patients that smoking is associated with MS susceptibility, said lead study author Zongqi Xia, MD, PhD, of Brigham and Women's Hospital in Boston.

The work, presented at the American Neurological Association's annual meeting, did not find an association between infectious mononucleosis and risk of MS, which was of interest because past studies have linked MS to exposure to Epstein-Barr virus which causes infectious mononucleosis.

The investigators found the incidence of MS in this population to be 123 per 100,000 -- a rate that is 20 to 30 times higher than that of the general population, Xia said. Consequently, the model holds promise for identifying individuals at the highest risk of developing MS who could be good candidates for prevention efforts.

"There is a great unmet medical need, which is there is currently no primary prevention strategy for multiple sclerosis," Xia said. This is due to several factors, he said, including that the risk factors and incidence of MS in a high-risk population are not well characterized. In addition, he said, "We do not have a good, reliable set of tools to identify those high-risk individuals, particularly at an early stage of the disease."

Through the Genes and Environment in Multiple Sclerosis (GEMS) project, Xia said he and his colleagues hope to establish a platform to map a sequence of events that lead to the onset of disease, capturing the transition from good health to disease state. Their ultimate goal, he said, is to test primary prevention strategies in this population.

Xia and colleagues created a formula to assess each study participant's Genetic and Environmental Risk Score (GERS), which incorporates presence of 64 genetic variants reported to have an association with MS, as well as three environmental factors reportedly associated with MS: female gender, smoking status, and history of infectious mononucleosis.

Source: MEDPAGE TODAY, http://www.medpagetoday.com/MeetingCoverage/ANA/53892, by Karen Blum, 04/10/15