Skip to main content

MS News Archive April 2015

Cytokines may play major role in MS (29/04/15)
Researchers say they have discovered the role of a major cytokine in multiple sclerosis that could be a target for new therapy against the disease.

MS is caused by immune cells that activate a cascade of chemicals in the brain, attacking and degrading the insulation that keeps neuronal signals moving. These chemicals, called cytokines, drive the inflammation in the brain, attracting more immune cells, and so causing the condition.

Researchers have long debated which cytokines drive the condition and which are merely accessory. Now a study published in the Journal of Immunology confirms the cytokine GM-CSF (Granulocyte macrophage colony-stimulating factor) likely plays an important role in human disease and offers a new explanation for why the MS treatment interferon-Beta is often so effective.

"After our animal studies showed GM-CSF was important in the development of an MS-like disease, we were excited to see these results confirmed using samples from MS patients in the current study," says Abdolmohamad Rostami, M.D., Ph.D., Chair of the Department of Neurology at Thomas Jefferson University and director of its neuroimmunology laboratory.

A few years ago, MS researchers were focused on a new type of immune cell called the Th-17 cell, which appeared to be a key player in driving the neuronal damage in MS. Because Th-17 cells produce the cytokine IL-17, researchers likewise thought this chemical was essential to the condition. IL-17, however, turned out to be something of a red herring.

In a paper published in Nature Immunology in 2011, Dr. Rostami and colleagues showed the Th-17 cells also produced another cytokine called GM-CSF, which created a chain reaction with another cell type ultimately increasing the GM-CSF levels in the brain of mouse models significantly. In addition, the researchers showed that in experimental models of MS, mice that were unable to produce GM-CSF never developed the condition, whereas mice lacking IL-17 did develop the disease, though generally developed a milder form.

In the new study, to test whether the same observation was true in humans, Dr. Rostami and colleagues tested blood samples of patients with MS who had not yet received therapy, and those currently being treated with interferon-Beta, a commonly used therapy. On average, untreated patients had two to three times as many immune cells producing GM-CSF as did patients being treated with interferon-Beta, or normal subjects. In addition, the researchers looked at brain samples of deceased patients with MS and found increased numbers of GM-CSF-producing cells in comparison to normal brain samples.

"The study demonstrates a new mechanism of action for interferon-Beta therapies," says Dr. Rostami.

In addition, a recent Phase 1 clinical trial of an antibody that blocks GM-CSF showed early signs of effect. Phase 1 trials are typically only designed to determine if a new drug is safe, and can't answer whether a new drug works. However, these results together with the work from the Rostami lab suggest that GM-CSF is a target worth pursuing for the treatment of MS.

"We hope that this research showing GM-CSF is an important target will lead us toward therapies that more effectively block the damaging immune reaction in the central nervous system of MS patients," says Dr. Rostami.

Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (29/04/15) 

Peripheral blood T cell dynamics predict relapse in MS patients on Fingolimod (29/04/15)


Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.

Methods/Principal Findings

Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7+CD45RO+) cells (TCM) and naïve T (CCR7+CD45RO-) cells decreased significantly, while those of effector memory T (CCR7-CD45RA-) and suppressor precursor T (CD28-) cells increased in both CD4+T and CD8+T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4+CD25highCD127low) cells in CD4+T cells and CCR7-CD45RA+T cells in CD8+T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4+TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4+T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4+T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (pcorr=0.0834).


The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

Source: PLOS One (29/04/15)

Scientists discover potential new treatment for MS (27/04/15)
Scientists from the Gladstone Institutes have discovered a way to prevent the development of multiple sclerosis in mice. Using a drug that blocks the production of a certain type of immune cell linked to inflammation and autoimmunity, the researchers successfully protected against the onset of MS in an animal model of the disease. The scientists say the next step is to test this strategy using other autoimmune disorders.

"We are very excited about these findings," says Eric Verdin, MD, a senior investigator at Gladstone and co-senior author on the study.

"In light of the significant effect the treatment had on inflammation, the implications of these results will likely extend beyond multiple sclerosis to other types of autoimmune disorders. We are particularly interested in testing this in type I diabetes given the similar pathways involved, and we are already seeing very promising results in preliminary experiments."

In the immune system, two kinds of T cells strike a delicate balance - T helper cells (Th17) activate the immune system, protecting against infections and cancers, while regulatory T cells (Tregs) suppress the system, keeping it in check. A disparity between these cell types, where there are too many Th17 and not enough Tregs, can lead to a hyperactive immune system, resulting in inflammation, tissue damage, and autoimmune disease.

In the current study, published in the Journal of Experimental Medicine, the researchers discovered that an important regulatory protein, sirtuin 1 (SIRT1), is involved in the production of Th17 cells. By blocking this protein, the scientists can protect against the onset of autoimmunity. SIRT1 also has a negative impact on Treg maturation and maintenance, so inhibiting its expression simultaneously enhances the production of Tregs and suppresses the creation of Th17.

To test this effect on disease, the researchers used a mouse model of MS and treated the animals with a drug that inhibits SIRT1. Typically, MS-model mice experience severe motor problems, eventually leading to paralysis, but when they were given the drug the mice behaved perfectly normally. Moreover, the treated animals showed no signs of inflammation or cell damage in their spines, classic markers for MS.

In contrast with the current research, SIRT1 is typically thought of as having anti-inflammatory properties, and compounds that increase SIRT1, like resveratrol, have been proposed as a way to delay aging. However, first author Hyungwook Lim, PhD, a postdoctoral fellow at Gladstone, says the new research suggests that the protein's effects are more complicated.

"The conventional theory has been that you should activate SIRT1 to improve health and longevity, but we show that this can have negative consequences," says Dr. Lim.

"Instead, we think the role of SIRT1 very much depends on the type of tissue being targeted. For instance, in immune cells, instead of being anti-inflammatory SIRT1 appears to have a pro-inflammatory role, which makes it a prime target to treat autoimmune disorders."

Other Gladstone investigators on the study include Jae Kyu Ryu, Mingjian Fei, Intelly Lee, Kotaro Shirakawa, Herbert Kasler, Hye-Sook Kwon, Katerina Akassoglou, and Melanie Ott, who was a co-senior author on the paper. Scientists from the University of California San Francisco, Scripps Research Institute, Buck Institute for Research on Aging, National Institute of Infectious Diseases Japan, German Cancer Research Center, New York University School of Medicine, and Howard Hughes Medical Institute also took part in the research. Funding was provided by the Kurtzig and Mulholland families, the National Center for Research Resources, and the National Center for Biotechnology Information.

Source: EurekaAlert Copyright © 2015 by the American Association for the Advancement of Science (AAAS)(27/04/15)

MS drug breakthrough by French firm (27/04/15)
French biotechnology company MedDay has announced encouraging results for a multiple sclerosis drug trial, saying it decreased its progress and in some cases led to a “significant improvement” for patients.

“This is the first time a drug has been able to decrease the rate of disease progression in addition to improving a significant proportion of patients with progressive MS," said MedDay CEO Frederic Sedel in a statement.

The experimental drug MD1003 has undergone Phase III clinical trial, the last stage before filing for authorisation to market the drug in the treatment of primary and secondary progressive multiple sclerosis.

The results of the study, presented to the annual meeting of the American Academy of Neurology, were encouraging, said Professor Ayman Tourbah, the study's principal investigator.

“The rapid rate of recruitment into this multi-centre study illustrates the serious need for a well-tolerated drug by patients with primary and secondary progressive multiple sclerosis,” he added in the company's statement.

“The significant proportion of patients showing improvement at twelve months, coupled with the decrease in risk of disease progression demonstrated here, makes MD1003 a potentially important new therapy for patients and in the field of MS.”

The application process to license the drug will begin when all the test results are in, expected by the end of the year.

Source: Malaymail Online Copyright © 2015 Malay Mail Online (27/04/15)

Study highlights ‘alarming rise’ in price of drugs (27/04/15)
There has been an “alarming rise” in the cost of multiple sclerosis treatments over the past dozen years and the cost of these drugs increased at rates well beyond the overall growth in prescription drug prices, according to a new study.

Reporting on the Pharmalot medical blog, Ed Silverman says the study found costs for three older medicines, which were launched between 1993 and 1996, rose by statistically significant amounts after a new type of treatment became available in 2002.

And a similar pattern of rising costs continued as still newer medications were approved by regulators between 2010 and 2013, according to the study, which appears in the Neurology medical journal.

“Instead of dropping back or stabilising as newer drugs became available, the prices for older medicines continued to rise, notably for the older medications,” says Dennis Bourdette, who chairs the neurology department at Oregon Health & Science University and is a co-author of the study.

“You would think more new drugs would lower the rate of the increases, but that didn’t happen.”

The study also compared prices paid by Medicaid, the U.S. Department of Veterans Affairs and government purchasers in Canada, the U.K. and Australia. Although Medicaid receives discounts, the costs for the multiple sclerosis treatments were often more than 70 per cent lower in the other countries than what was paid by Medicaid. The VA, meanwhile, paid 36 per cent less, on average, than Medicaid.

The findings are the latest attempt to track rising costs for prescription medicines. Until now, the discussion has largely focused on treatments for hepatitis C, and cancer, as well some generic drugs. Bourdette says this is the first effort of its kind by neurologists to highlight the upward trend in multiple sclerosis drug costs.

The study examined pricing data for nine multiple sclerosis treatments – including older injectable medicines and newer oral drugs – between 1993 and 2013. The researchers also compared prices for the older drugs with another group of injectable medicines used to treat rheumatoid arthritis that were available during this time and found price hikes were much higher for the MS drugs.

More specifically, the study found three so-called first-generation MS treatments, which originally cost between $8,000 and $11,000 annually, now cost about $60,000. This worked out to an average increase of 21 per cent to 36 per cent annually for these three injectable drugs, which include Betaseron, which is sold by Bayer, Avonex, marketed by Biogen, and Copaxone, a big seller for Teva Pharmaceutical.

The cost increases for these drugs corresponded with the 2002 approval of Rebif, which is sold by Merck Serono, according to the study. And the trend continued with still newer oral drugs that were approved by the FDA between 2010 and 2013. These newer meds included Gilenya, which is marketed by Novartis, Aubagio, sold by Sanofi’s Genzyme unit, and Tecfidera, another Biogen medicine.

A Teva spokesman said pricing is competitive to other brand-name drugs and reflects investment to research, develop and sell a safe and effective product. A Bayer spokesman told Silverman that Betaseron pricing reflects its “value” and is “comparably” priced. A Biogen spokesman, meanwhile, said the drug maker provides discounts and revenues are used to fund research for new drugs.

Meanwhile, prices for the newer oral medications rose eight per cent to 17 per cent annually since their approvals over the past few years compared with overall prescription drug inflation of three-five per cent, according to the study.

“If the prices for the older drugs hadn’t been raised so dramatically, the newer drugs would have had a more difficult time pricing them as high as they did,” says Bourdette. “These companies didn’t have to price them at a lower level, because the prices for the older drugs were steadily being increased. What they’re doing is feeding off each other in terms of how the prices are set.”

Source: The Wall Street Journal Copyright ©2015 Dow Jones & Company, Inc (27/04/15)

Study finds brain atrophy reduces in Lemtrada patients (24/04/15)
Genzyme has announced new magnetic resonance imaging (MRI) data from the Lemtrada clinical development program.

In relapsing remitting multiple sclerosis (RRMS) patients treated with Lemtrada in the Phase III pivotal studies, MRI effects observed in the two-year trials were maintained through two additional years in the extension study (years three and four). After the initial two courses of treatment in the pivotal studies, which were given at month zero and at month 12, approximately 70 percent of Lemtrada patients did not receive additional Lemtrada treatment during the following three years, through month 48.

The Phase III trials of Lemtrada were randomized, two-year pivotal studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had an inadequate response to another therapy (CARE-MS II).

Through year four, the adverse event profile of Lemtrada was consistent with that observed during the pivotal studies. The new data includes:

The rate of brain atrophy, as measured by brain parenchymal fraction (BPF), decreased progressively over four years among Lemtrada patients in CARE-MS I. Among CARE-MS II Lemtrada patients, the rate of brain atrophy decreased progressively over three years and remained low in year four. In both studies, the median yearly brain volume loss was less than -0.20% in years three and four, which was lower than what was observed during the two-year pivotal studies.

In CARE-MS I and II, treatment with Lemtrada significantly reduced the risk of developing new lesions compared to interferon beta-1a. In the extension study, most of the Lemtrada-treated patients from CARE-MS I and II were free of new lesions and MRI activity in years three and four (approximately 70%).

Brain atrophy is a measure of the most destructive pathological processes that occur in MS.1 It is seen from the earliest stages of disease and may lead to irreversible neurological and cognitive impairment. Given its association with disability, control or prevention of brain atrophy is an important target for MS treatment. In addition, MRI measures including lesion activity are considered useful tools when evaluating the effect of MS therapies, and lesion activity is among several prognostic factors for unfavorable clinical outcomes.

“It is very promising that most Lemtrada patients experienced slowing of brain atrophy and remained free of new lesions despite receiving their last treatment course three years previously,” said Dr. Alasdair Coles, Professor, Department of Clinical Neurosciences, University of Cambridge. “These new MRI data are consistent with the clinical data from the extension study that provide additional evidence of the sustained efficacy of Lemtrada on both relapses and disability.”

Safety results from the second year of the extension study were previously reported. No new risks were identified. The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Other serious side effects associated with Lemtrada include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis. A risk management program incorporating education and monitoring helps support early detection and management of these identified risks.

“The four-year MRI data support the prolonged efficacy of Lemtrada,” said Genzyme President and CEO, David Meeker, M.D. “These results are encouraging, as they provide further evidence of Lemtrada’s potential to change the treatment approach for people living with relapsing forms of MS.”

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. MRI scans were taken at CARE-MS baseline, and at 12, 24, 36 and 48 months.

In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

Source: Market Watch Copyright ©2015 MarketWatch, Inc (24/04/15)

Cooling device ‘not associated with changes in performance’ (24/04/15)
Patients with multiple sclerosis (MS) often have sensitivity to heat that worsens their symptoms.

In earlier studies with MS patients a device system that cools body temperature by chilling one palm proved useful in helping them walk faster and longer.

But in a study reported during a poster session April 22 at the 2015 American Academy of Neurology annual meeting in Washington, DC, a California team of researchers found that having the device did not motivate patients to walk more.

Andrew Dorsch, MD, and colleagues at the University of California Los Angeles Health System recruited 24 ambulatory MS patients with heat sensitivity for the study. The subjects were fitted with wireless sensors. They were worn for a week to get a baseline level of physical activity. The patients were then randomly assigned to get either the device or a sham device.

The hope was that the patients with the cooling device would increase their level of exercise. But that did not happen. “Use of a hand-held cooling device was not associated with changes in walking performance,” the team wrote.

But they did find that wireless health technologies are useful in measuring such activities.

Source: MD All Specialities Copyright HCPLive 2006-2015 Intellisphere, LLC (24/04/15)

Alcohol consumption linked to lower MS disability (24/4/15)
Multiple sclerosis patients who consumed larger amounts of alcohol had lower rates of disability per the Expanded Disability Status Score (EDSS) and Multiple Sclerosis Severity Score (MSSS), a new study indicates.

Consumption of beer also affected EDSS scores positively; however consumption of wine had no association with EDSS score, according to Camilio Diaz-Cruz, MD, of Brigham and Women's Hospital in Boston, who reported the findings at the American Academy of Neurology 2015 Annual Meeting.

Camilio and colleagues measured alcohol/wine consumption in servings per week for 908 patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study. Drinking habits were also assessed, and influence of alcohol or wine consumption on clinical outcomes was assessed using regression models for relapse rate in the past year, and concurrent EDSS and MSSS outcomes. Associations with and changes in Symbol Digit Modality Tests (SDMT) were also assessed in a subset of patients.

There were 56 nondrinkers in the cohort; 98 of who preferred spirits, 249 preferred beer, 283 preferred red wine, and 222 favoured white wine. Median alcohol intake was 1.1 servings per week.

Those who had higher alcohol intake were significantly associated with lower EDSS and MSSS. Both red and white wine had a non-significant negative association with both EDSS and MSSS, and there was no significant association between alcohol or wine consumption and relapse rate in the past year, change in EDSS or MSSS over one year, current SDMT score, and change in SDMT score in the last year. Notably, beer drinkers tended to have lower EDSS, however the relationship was weaker compared to that of “hard liquor”.

Although further data analyses are required to better understand the potential cause-effect relationship and underlying mechanism, the findings are complimentary to several previous but unconfirmed studies that suggest alcohol may be neuroprotective in the risk of developing multiple sclerosis.

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (24/4/15)

Early treatment with Copaxone ‘benefits patients’ (24/04/15)
Teva has announced new data on the safety and efficacy of Copaxone (glatiramer acetate injection) 40mg/mL in patients with relapsing forms of multiple sclerosis (MS).

In the 36-month placebo-controlled and open-label extension phases of the Glatiramer Acetate Low-frequency Administration (GALA) study, outcomes of early start (ES) patients who received three-times-a-week Copaxone 40mg/mL for 36 months were compared to delayed start (DS) patients who initiated Copaxone after the 12-month placebo-controlled phase of the trial. The adjusted mean annualized relapse rate was significantly lower for the ES patients over 36 months and early treatment was associated with a sustained reduction in lesion activity and the evolution of active lesions to chronic black holes.

Copaxone is indicated to reduce the frequency of relapses in patients with relapsing-remitting MS, including those who have experienced a first clinical episode and have MRI features consistent with MS.

Source: MPR Copyright © 2015 Haymarket Media, Inc (24/04/15)

Alcohol consumption linked to lower MS disability (24/04/15)
Multiple sclerosis patients who consumed larger amounts of alcohol had lower rates of disability per the Expanded Disability Status Score (EDSS) and Multiple Sclerosis Severity Score (MSSS), a new study indicates.

Consumption of beer also affected EDSS scores positively; however consumption of wine had no association with EDSS score, according to Camilio Diaz-Cruz, MD, of Brigham and Women's Hospital in Boston, who reported the findings at the American Academy of Neurology 2015 Annual Meeting.

Camilio and colleagues measured alcohol/wine consumption in servings per week for 908 patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study. Drinking habits were also assessed, and influence of alcohol or wine consumption on clinical outcomes was assessed using regression models for relapse rate in the past year, and concurrent EDSS and MSSS outcomes. Associations with and changes in Symbol Digit Modality Tests (SDMT) were also assessed in a subset of patients.

There were 56 nondrinkers in the cohort; 98 of who preferred spirits, 249 preferred beer, 283 preferred red wine, and 222 favoured white wine. Median alcohol intake was 1.1 servings per week.

Those who had higher alcohol intake were significantly associated with lower EDSS and MSSS. Both red and white wine had a non-significant negative association with both EDSS and MSSS, and there was no significant association between alcohol or wine consumption and relapse rate in the past year, change in EDSS or MSSS over one year, current SDMT score, and change in SDMT score in the last year. Notably, beer drinkers tended to have lower EDSS, however the relationship was weaker compared to that of “hard liquor”.

Although further data analyses are required to better understand the potential cause-effect relationship and underlying mechanism, the findings are complimentary to several previous but unconfirmed studies that suggest alcohol may be neuroprotective in the risk of developing multiple sclerosis.

Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (24/04/15)

MRI patterns decipher between MS and VWM (23/04/15)
Researchers say they have found evidence that makes it easier to differentiate between multiple sclerosis (MS) and vanishing white matter disease (VWM) – conditions that can show considerable similarities.

According to a presentation at the American Academy of Neurology in Washington, DC, diagnosing primary and secondary progressive multiple already presents a challenge because the signs – like large and confluent lesions and multiple cavitary lesions – are rarely shown on a brain MRI. However, the comparable symptoms with VRM can cause a misdiagnosis.

“It is important to identify specific MRI findings that can be relevant diagnostic tools,” the study’s authors wrote.

Lead author Xavier Ayrignac, of the Department of Neurology in Centre Hospitalier Universitaire de Montpellier in France, and his colleagues evaluated 14 MS and 14 VWM patients to find key differences between their brain scans.

“In this context, the diagnosis of multiple sclerosis can be difficult and a diagnosis of VWM should be considered,” Ayrignac and his team determined.

When cavitary lesions show up on the MRI, it becomes more challenging to decipher between the central nervous system diseases. The researchers focused on specific features including regional atrophy, white matter and gray matter hyperintensities location and type, and posterior fossa involvement along with middle cerebellar peduncle and cerebellar white matter lesions.

While similar results were indicated between the MS and VWM patients – like focal atrophy, basal ganglia atrophy, and corpus callosum atrophy – the investigators found important individualized characteristics for the diseases:

- Cerebellum atrophy: 8 (57%) MS patients, 13 (93%) VWM patients
- Topography of the lesions (thalamus): 10 (71%) MS patients, 1 (7%) VWM patients
- Topography of the lesions (midbrain): 11 (79%) MS patients, 4 (29%) VWM patients
- Extensive juxtacortical lesions: 7 (50%) MS patients, 14 (100%) VWM patients
- Ovoid perpendicular to the ventricle: 14 (100%) MS patients, 0 VWM patients
- Corpus callosum extensive: 9 (64%) MS patients, 14 (100%) VWM patients
- Extensive lesions (external capsule): 4 (29%) MS patients, 12 (86%) VWM patients
- Perivascular cavitary lesions: 10/12 (83%) MS patients, 1/6 (17%) VWM patients
- Infratentorial symmetrical: 0 MS patients, 6/12 (50%) VWM patients
- Fluid like cavitary lesions: 3 (21%) MS patients, 9 (64%) VWM patients

“Nevertheless, our results suggest that the analysis of characteristics of MRI findings including topography and morphology of the lesions is of major diagnosis importance for the differential diagnosis of these 2 disorders,” the team concluded.

Source: MD All Specialities Copyright HCPLive 2006-2015 Intellisphere, LLC (23/04/15)

Team shows how blood-brain barrier is maintained (23/04/15)
In a new study, researchers have made insights into how the blood-brain barrier (BBB) - which allows only selected molecules to pass through - is maintained, identifying a protein key to the process. Delivering this protein to mice with the rodent equivalent of MS improved their symptoms.

In certain diseases, however, such as multiple sclerosis, the barrier can be improperly breached. These "leaks" can allow immune cells and inflammatory molecules to pass through, causing inflammation that leads to neuronal damage.

The research, led by the University of Pennsylvania's Jorge Ivan Álvarez and Cornelia Podjaski of McGill University and Alexandre Prat of the University of Montreal, will appear in the journal Brain.

Alvarez, an assistant professor in Penn's School of Veterinary Medicine, conducted the study with Podjaski and Prat and colleagues from McGill University and from the University of Montreal.

In 2011, Alvarez and Prat published a study in Science that showed that the protein sonic hedgehog, or Shh, is secreted by central nervous system cells called astrocytes and plays a key role in blood-brain barrier maintenance, in part by preventing immune cells from entering the brain. But the researchers still didn't have a complete picture of the signaling events downstream of Shh that mediated this effect. To learn more, they first used human cells in culture from the blood-brain barrier, called endothelial cells. They found that applying Shh to the cells caused levels of a protein called netrin-1 to rise.

In mice bred to lack the molecular receptor for Shh, netrin-1 expression was reduced, indicating that netrin-1 expression depends on Shh.

"Netrins are best known to play a role in guiding the direction of axon growth as well as morphogenesis and tissue formation," Álvarez said. "But our work suggested a new role for netrin-1 in the blood brain barrier."

Curious as to whether this might influence MS, they examined BBB cells from the brains of people who had died from the disease. Normal tissue from these individuals contained low levels of netrin-1, while the diseased lesions in the brain had higher levels. The researchers found similar results in a mouse model of MS called experimental autoimmune encephalomyelitis, or EAE.

Next, the team directly measured netrin-1's effect on BBB permeability by labeling tracer molecules and found that netrin-1 significantly reduced the movement of molecules across cultures of human BBB endothelial cells. Further experiments showed that netrin regulates this process by promoting the expression of the so-called "tight junction" proteins, which are located between BBB endothelial cells and are responsible for controlling barrier function. The team also found that, when in an environment rife with inflammatory signaling molecules, which would normally compromise the integrity of the BBB, netrin-1 had a counteracting effect, preventing disruption to the BBB.

"In mice bred to lack netrin-1, we observed that proteins normally found in the blood accumulated in the animals' brain, another sign that netrin-1 ensured the integrity of the BBB," Podjaski said.

Armed with these findings suggesting netrin-1 protects the BBB, the team tested the potential of netrin-1 in ameliorating EAE symptoms, which are similar to those of people with MS.

"By administering netrin-1 to mice before the EAE disease was induced, we found that animals had less severe disease, delayed disease onset, fewer lesions in their brain, fewer markers of inflammation and better maintenance of body weight compared to mice given a sham treatment," Podjaski said.

"In mice, we found the disease outcome is better when they're treated with netrin-1, even when delivered after disease processes had begun," Alvarez said. "And all those observations held up in vitro as well."

Moving forward, the researchers hope to further elucidate the pathway through which Shh and netrin-1 operate, with an aim toward finding more effective ways to uphold the barrier and perhaps one day treat diseases like MS.

"We now know that Sonic is above netrin-1 in the signaling pathway, but what else is Sonic hedgehog doing?" Prat said. "We need to complete the puzzle with Sonic first to give us better therapeutic strategies."

Source: Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (23/04/15)

Remyelinating antibody study data revealed (23/04/15)
Acorda Therapeutics Inc has presented data from a Phase 1 clinical trial of rHIgM22, a remyelinating antibody being studied for the treatment of multiple sclerosis.

Safety data showed rHIgM22 was well-tolerated in each of the five tested doses, supporting additional clinical development. In addition, testing detected rHIgM22 in cerebrospinal fluid (CSF), indicating the drug’s access to the central nervous system.

These data were presented at the 67th American Academy of Neurology Annual Meeting in Washington, DC.

“In this study, rHIgM22 was well-tolerated over the full range of dose levels tested. Furthermore, we were able to verify that rHIgM22 is present in the CSF, showing that the antibody is available to the brain,” said Anthony Caggiano, M.D., Ph.D., Acorda’s Senior Vice President of Research and Development.

“We plan to advance our clinical program based on this data. The next study will include patients experiencing acute relapses. The combined results of these two studies will inform subsequent trials, which we anticipate will enrol both stable patients and those experiencing active relapses.”

This was a placebo-controlled, single-dose, escalating study in 72 patients with clinically stable MS to explore dose tolerability for six months after treatment. rHIgM22 was well-tolerated at all doses tested, with no safety signals identified. There were no dose-limiting toxicities and no serious adverse events in any of the five rHIgM22 dose levels in the study. The data presented included the concentration of rHIgM22 in the CSF at two days and four weeks after IV infusion. The antibody was measured at levels expected for antibodies of this class. There were no significant changes from baseline in clinical measures including MRI, magnetic resonance spectroscopy, Expanded Disability Status Scale, Timed 25-Foot Walk, and low contrast visual acuity.

The most commonly observed adverse events (>5% in the combined rHIgM22 treatment groups) reported in the study were: headache, contact dermatitis, multiple sclerosis relapse, infusion site hematoma, fatigue, arthralgia, back pain, muscular weakness, neck pain, pain in an extremity, pruritus, contusion, and flushing. No participants withdrew due to adverse events. No safety signals were identified by standard clinical MRI evaluations, or standard clinical, laboratory or ECG assessments.

Source: Finances © 2014 Finances International Ltd (23/04/15)

Increasing Tysabri dosing interval may cut PML risk (23/04/15)
Freedom from relapse was maintained in multiple sclerosis patients on Tysabri who received the infusion drug less frequently than the recommended 4-week interval, with lower risk of progressive multifocal leukoencephalopathy (PML), preliminary results from an ongoing analysis have indicated.

Among 886 patients treated with "extended" dosing at 10 American MS centers, the mean annualized relapse rate was the same at 0.1 per year as in 1,078 patients receiving Tysabri at the standard 4-week interval, according to Lana Zhovtis-Ryerson, MD, of NYU Langone Medical Center in New York City. MRI lesions counts were also similar.

Although patients testing positive for the JC virus - the pathogen whose reactivation triggers PML, a sometimes fatal brain inflammation - comprised 59 per cent of the extended dosing group, none have so far developed PML, she reported to the American Academy of Neurology's annual meeting.

With a total of 1,023 patient-years of exposure to Tysabri in this JC-positive subgroup, published risk algorithms show an expected incidence of 2.5 cases, Zhovtis-Ryerson and colleagues calculated.

At this point the finding of zero cases with extended dosing is not statistically significant, the researchers cautioned - but if the exposure reaches 1,248 patient-years with still no cases, it will be significant.

Meanwhile, two PML cases have developed in the standard-dosing group, among whom 41 per cent are JC-positive and who have received a mean of 30 Tysabri doses (SD 22).

Brian Weinshenker, MD, of the Mayo Clinic, who was not involved with the study, told MedPage Today the approach deserves more study but urged caution in adopting it clinically.

He noted if just one patient in the extended dosing group developed PML, "it would have completely negated any trend to reduced risk."

PML has been the primary concern with Tysabri almost since it was introduced in 2004. When several cases turned up shortly after its approval, the drug was withdrawn for some months, then relaunched with a restricted distribution program that included clinician and patient education on the risk.

The question of how to reduce PML risk with Tysabri, which exceeds one per cent in patients positive for JC virus and who have two other risk factors (treatment duration and history of immunosuppressant therapy), has occupied MS neurologists since the relaunch. Most studies have shown patients who discontinue the drug or take long "holidays" experience a spike in relapse risk. Switching to another drug has not prevented such spikes because a months-long washout period after Tysabri discontinuation is needed before starting a different agent.

Some clinicians have been experimenting instead with longer dosing intervals, in the belief that the four-week schedule keeps the drug's target - alpha4beta1 integrin, an adhesion molecule involved in immune cell trafficking - so saturated that JC virus immune surveillance is eliminated. Extending the interval may relax the immune suppression just enough to keep latent JC virus under control while still maintaining the anti-relapse effect.

In the current study, Zhovtis-Ryerson and colleagues sought to capture this empirical experience by canvassing centers that have adopted the strategy with some patients.

They defined extended dosing as any interval from 31 days up to 61 days. They further subdivided the extended dosing patients into those with early extended dosing and late extended dosing. Another 309 patients had dosing that varied and could not be classified into either of those groups.

Patients in the extended dosing groups were at somewhat higher risk for PML than those treated at the recommended interval, with a higher proportion testing positive for JC virus, more patients with a history of immunosuppressant therapy (18 per cent versus 11 per cent), and more total Tysabri doses (mean 39 versus 30). Patient age, disease duration, and gender balance did not differ markedly between standard and extended dosing groups, however.

Among extended dosing patients, the mean duration of that schedule was 23 months overall. These varied only modestly between the early, late, and variable dosing regimens.

Treatment efficacy (Tysabri 's forte) was excellent irrespective of dosing interval. Some 65 per cent of standard and 65 per cent of extended dosing groups showed no evidence of disease activity (NEDA). That is, no active MRI lesions and no clinical activity. The variable extended dosing group suffered a little bit in this respect, with 55 per cent meeting the NEDA standard compared with about 70 per cent for both early and late dosing.

Weinshenker commented that selection of patients for extended dosing, which was not random, might have involved "biases against committing more aggressive MS patients on the extended interval program, which might reduce the ability of the investigators to detect reduction in efficacy."

Nevertheless, he said, extended dosing "is a promising and sensible approach that might turn out to be effective."

Zhovtis-Ryerson and colleagues have established a registry called EXTEND to which other clinicians may contribute, at They are also planning a prospective study to examine effects of the different regimens on disability progression over time.

The study had no external funding and authors declared they had no financial interests relevant to the work.

Source: Medpage Today © Medpage Today 2015 (23/04/15)

Hospital visits for paediatric MS Patients continue to climb (23/04/15)
Although the number of paediatric patients with multiple sclerosis has increased over the years, researchers recently revealed one of the first studies to offer population-based information.

Data from the Paediatric Health Information System (PHIS) has been presented at the 2015 annual meeting of the American Academy of Neurology in Washington, DC. Lead author Amy M. Lavery, MSPH, and her Department of child neurology in the Children’s Hospital of Philadelphia colleagues worked to shed light on a subject that doesn’t have a firm backing of research results.

The authors wrote that since “literature is lacking with respect to overall disease” when it comes to paediatric MS, it was time to “examine the prevalence of hospital admissions.”

From 2004 to 2013, the database revealed inpatient visits, emergency department encounters, and charges encountered from 44 children’s hospitals in the United States. The findings showed a trend in hospital visits among the affected children.

The 1,422 patients – made up of twice as many females – found in the database collectively had 2,068 hospital encounters and stayed for an average of 4 days. In 2004 paediatrics MS patients checked into the hospital an average of 2.37 times, however, that number jumped to 4.13 in 2013. Also, for every 10,000 hospital check-ins the cause associating with MS has increased from 3.47 to 5.95. The reason behind the rate surge, the authors noted, could be attributed to the addition of paediatric MS centres and awareness.

“A test for trend showed a steady, significant increase in encounters for MS,” the team said, which raises the question if that number will continue to grow. For children ages 11 and younger, the amount of MS cases has stayed the same while ages 11 to 15 and 15 and older has steadily increased. This study may be one of the first to address paediatric MS hospitalisations, however, it won’t be the last.

“Further analyses will incorporate pharmacy data and investigate factors contributing to healthcare utilization and hospital admission rates,” the study concluded.

Source: MS All Specialities Copyright HCPLive 2006-2015 Intellisphere, LLC (23/04/15)

Doctor offers new model for MS (22/04/15)
Multiple sclerosis may be more of a continuum than three distinct types of disease, and a new model attempts to capture that nuance reports MedPage Today.

The "topographical" model could provide a new way of looking at disease course, Stephen Krieger, MD, of Mount Sinai in New York City, claims.

"There's thought that MS is more of a continuum," Dr Krieger said.

"We should not think in terms of those categories, but we should think of it as a mixture of relapses and progression and how specifically they mix together."

Currently, MS is classified as being in one of three groups: relapsing-remitting, secondary progressive, and primary progressive. But Dr Krieger, a protege of Fred Lublin, MD, who created the three-category model, said the system doesn't accurately capture the range of disease.

"There's real diagnostic uncertainty," Dr Krieger told MedPage Today.

"It takes us years to figure out which category someone is in. A lot of progressive patients stay like they are for years. You're not always sure which category someone fits into, nor do those categories tell us how someone's disease is going to progress."

For his new model, which Dr Krieger calls a "true admixture of inflammation and progression" that describes the clinical course of MS in a more biologically informed way, he incorporated five factors: topographical distribution of lesions and the relapses they cause, relapse frequency, relapse severity, relapse recovery, and progression rate.

It essentially suggests the clinical manifestations of MS are a consequence of the interplay between inflammatory lesions - the relapsing part of the disease - and generalised loss of functional capacity, as seen in the progressive part of the disease.

To illustrate the concept, Dr Krieger came up with a peak-and-pool model. There's a shallow end that drops off into a deep end, where the shallow end represents the spinal cord and optic nerve, the mid-section represents the posterior fossa, and the cerebral hemispheres constitute the deep end.

At the same time, brain lesions appear as topographic peaks that rise from the floor of the pool. The water's surface is the clinical threshold, and when the central nervous system lesions' peaks cross it, a relapse or flare occurs.

Disease progression is represented by a falling water level, which essentially represents a loss of neurons and declining brain volume, something that can be measured on MRI, Dr Krieger said. The model also implies progression could take the form of relapses as these peaks start to rise above the water, Krieger said.

The very visual disease representation was the result of a pro bono collaboration with Harrison and Star, a healthcare communications company.

When asked what his mentor Lublin thought about the challenge to his work, Dr Krieger said he's been "incredibly supportive."

"He thinks it's really interesting, and he wants to see me make it into an applied model for prediction," Dr Krieger said.

"We'll try to operationalise it over the coming couple of years and figure out how to do precise metrics. We'll figure out how to take a clinical trial database and apply that and figure out things we otherwise couldn't."

Source: MedPage Today © 2015 MedPage Today, LLC (22/04/15)

Smoking ‘leads to multiple sclerosis treatment issues’ (22/04/15)
According to study results presented at the 2015 annual meeting of the American Academy of Neurology in Washington, DC, researchers say they have tied the effects of cigarette smoke with various health issues experienced by current and potential multiple sclerosis patients.

“In previous studies we demonstrated that rats exposed to cigarette smoke develop increased brain inflammation and oxidative stress,” lead author Walter Royal III, MD, and colleagues wrote in the presentation. “In these studies we examine the effects of cigarette smoke exposure on systemic and brain inflammatory responses in a murine model of MS, experimental allergic encephalomyelitis (EAE).”

The team analysed female mice under different conditions by splitting them up into one of the following groups:

Exposed to the smoke chamber but not cigarette smoke or induced to get EAE
Exposed to cigarette smoke but not induced to get EAE
Not exposed to cigarette smoke but induced to get EAE
Exposed to cigarette smoke and induced to get EAE
Not exposed to cigarette smoke or the smoking chamber (controlled group)

For the mice that were exposed to cigarette smoke (5 days per week for 4 weeks) the cigarettes contained the “regular” amount of nicotine (0.7 mg per stick and tar (9.4 mg per stick). Also, they were restrained and ventilated by the smoke machine. The mice were immunized with oligodendrocyte glycoprotein peptide fragment after one month of cigarette smoke exposure and after an additional two weeks their brains were removed for further evaluation.

The authors noted that the control group was under the same restraints but without the smoke.

From this examination the team found that in the mice induced to develop EAE, the ones who were also exposed to cigarette smoke had “significantly enhanced pro-inflammatory response, with increased levels of immune cell activation and cytokine secretion.” The smoke was associated with higher oxidative stress, as previous studies have suggested, and lower expression of Nrf2 as well. The researchers pointed out that in the mice with EAE exposed to cigarette smoke, the nuclear translocation of the transcription factor climbed.

“Such effects may contribute to the development of enhanced disease activity among individuals with MS, and, therefore, studies of the mechanisms and potential treatment of these effects are required the authors wrote.

The study authors concluded that cigarette smoke increases the risk of developing the disease while also making it more likely that treatment will fail.

Source: MD All Specialities Copyright HCPLive 2006-2015 Intellisphere, LLC (22/04/15)

Three year data on Plegridy revealed (22/04/15)
Biogen has announced new data from the ATTAIN study which demonstrate the long-term safety and efficacy of Plegridy over a three-year period in people with relapsing-remitting multiple sclerosis (RRMS). The interim results from the first year of ATTAIN, a two-year extension study of the Phase 3 study, show the benefits of continued Plegridy treatment on clinical outcomes and further define its safety profile.

“This data offers additional insights into the benefit-risk profile of Plegridy by demonstrating a consistent safety profile and continued efficacy over three years,” said Bruce Hughes, M.D., director of the Ruan Multiple Sclerosis Center at Mercy Ruan Neurology Clinic and Research Center in Iowa.

“Long-term safety and robust efficacy are important considerations when evaluating treatment options for this chronic condition.”

The most common side effects reported were injection site reactions and flu-like symptoms, the majority of which were mild or moderate. The rate of neutralizing antibodies was one percent after three years.

Source: Finances © 2015 Finances International Ltd (22/04/15) 

Study finds MS activity can return when treatment stops (22/04/15)
A new study by the NYU Langone Medical Centre found almost 40 per cent of patients had some disease activity return when they stopped taking their meds. The findings, issued in a press release by the centre, have been presented at the American Academy of Neurology Annual Meeting held April 18-25, in Washington, D.C.

"Despite long periods of disease stability while taking medication, we found a large minority of patients who stopped experienced relapses or disability progression," said lead study author Ilya Kister, MD, an assistant professor of neurology at the NYU Langone Multiple Sclerosis Comprehensive Care Center.

"We need to identify situations when it is safe for patients with MS to stop taking these medications."

Little is known about MS disease progression after first-line, disease-modifying therapies are discontinued in clinically-stable patients.

For the study, Dr. Kister and colleagues prospectively studied 181 patients from the global observational MSBase Registry, examining MS relapse rates and disability progression rates in patients who stopped taking disease-modifying therapy.

Patients in the study were aged 40 and older, had experienced no relapses and reported stable disability progression (measured by EDSS scores) for at least 5 years, and had been taking medication for at least three years. Once medications were ceased, patients were followed for at least three years.

After discontinuing medication, 24 per cent of patients experienced a clinician-reported relapse, 32 per cent sustained three-month disability progression, and 10.6 per cent of patients recorded both relapses and disability progression.

Researchers found 77 patients - or 42 per cent - restarted medication after an average of 22 months. Restarting medication was associated with a 59 per cent risk reduction of disability progression.

"Decisions regarding stopping disease-modifying therapy may have implications for short and long-term prognosis. We know a lot about what happens when therapy is started, but we know very little about what happens when therapy is stopped", said Dr Kister.

Dr Kister and colleagues are now calling for a randomised trial of discontinuation of disease-modifying therapy to provide more evidence of when exactly it might be safe for patients to stop taking their medications.

Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (22/04/15)

Mindfulness ‘as good as anti-depressants’ (21/04/15)
Mindfulness-based cognitive therapy may be as good as pills at stopping people relapsing after recovering from major bouts of depression, according to a new study.

Mindfulness-based cognitive therapy (MBCT) was developed from mindfulness techniques, which encourage individuals to pay more attention to the present moment, combined with cognitive behaviour therapy (CBT), specifically to try to help people who have recurring depression.

It teaches people to recognise that negative thoughts and feelings will return, but that they can disengage from them.

The trial, published in The Lancet involved a group of 424 adults from GP practices in the south-west of England, who were willing to try either the pills or the therapy. Half were randomly allotted to each. Those assigned to mindfulness had eight group sessions of more than two hours plus daily home practice and the option of four follow-up sessions over a year. The course involved mindfulness training, group discussion and cognitive behaviour exercises. The patients gradually came off their medication. Those assigned to the other group stayed on the tablets for two years.

The relapse rates in the two groups were similar, with 44% in the mindfulness group and 47% for those on the drugs. In each group there were five adverse events, including two deaths.

The researchers had thought the study might show that therapy was more effective than pills, based on their earlier work. Lead author Willem Kuyken, a professor of clinical psychology at the University of Oxford, said: “That was our hypothesis. It was based on our pilot study in 2008. There was a suggestion that MBCT might do better than medication. The reality is that it was not superior to medication.”

However, they established that mindfulness-based therapy is equally as good as drugs, which could offer a new option for those who do not want to be on medication for years. Co-author Prof Richard Byng, from the Plymouth University Peninsula Schools of Medicine and Dentistry, said: “Currently, maintenance antidepressant medication is the key treatment for preventing relapse, reducing the likelihood of relapse or recurrence by up to two-thirds when taken correctly.

“However, there are many people who, for a number of different reasons, are unable to keep on a course of medication for depression. Moreover, many people do not wish to remain on medication for indefinite periods, or cannot tolerate its side-effects.”

Nigel Reed, from Sidmouth, Devon, who took part in the trial, said: “Mindfulness gives me a set of skills which I use to keep well in the long term. Rather than relying on the continuing use of antidepressants, mindfulness puts me in charge, allowing me to take control of my own future, to spot when I am at risk and to make the changes I need to stay well.”

The study also showed that the therapy might work better than pills for those who have some of the most troubled histories and are at the highest risk of relapse. It was found to have protected people with increased risk because of a background of childhood abuse. The paper said: “Perhaps MBCT confers resilience in this group at highest risk because patients learn skills that address some of the underlying mechanisms of relapse or recurrence.”

Kuyken said he expected Nice to look at the study when it convenes shortly to revise its guidelines on recurrent depression.

Source: The Guardian © 2015 Guardian News and Media Limited (21/04/15)

Scientists target new painkillers from spider venom (21/04/15)
Scientists in Australia have made an important discovery about spider venom that could lead to a new class of painkillers.

Spiders use their venom to immobilize or kill their prey. Researchers from the University of Queensland isolated seven peptides—the building blocks of proteins—in spider venom that blocked the molecular pathway responsible for sending pain signals from the nerves to the brain. One peptide in particular, from a Borneo orange-fringed tarantula, had the right structure, stability and potency to potentially become a painkilling drug, the researchers said. The study was recently published in the British Journal of Pharmacology.

The medical community is eager to identify new medications to treat chronic pain, which affects about 15 per cent of all adults, according to a 2012 study published in the Journal of Pain. Traditional painkillers such as morphine and widely used medications like hydrocodone can be addictive, and abuse of the drugs has soared in recent years, prompting stricter regulations from the U.S. Drug Enforcement Administration.

“Spider venom acts in a different way to standard painkillers,” said Jennifer Smith, a research officer at the University of Queensland’s Institute for Molecular Bioscience. Dr. Smith, one of the authors of the Australian study, doesn’t expect a painkiller derived from the venom will be addictive because it blocks a specific channel that transmits pain to the brain. Opiate painkillers, by contrast, block widespread opioid receptors on cells in the brain, spinal cord and other organs.

Spiders aren’t the only venomous creatures with medicinal potential. Researchers in France have found ingredients in the venom from Africa’s black mamba snake, one of the world’s deadliest, had painkilling properties as potent as morphine. And a drug derived from the venom of the sun anemone, which lives on reefs in the Caribbean, is currently being tested in the U.S. on people with psoriasis and could also be used to treat other autoimmune disorders such as multiple sclerosis and rheumatoid arthritis.

Scientific interest in venom’s painkilling properties stems from an earlier discovery by geneticists of a rare mutation in some people—in a gene known as SCN9A—that eliminates their ability to feel pain. While they can experience touch, warmth and other tactile functions, their sense of smell and pain are inhibited, Dr. Smith said. Some venoms from spiders and other animals and plants have been found to mimic the effects of the gene mutation.

The Australian study analysed spider venom from 205 species found locally and in other countries (there are currently about 45,000 known species of spiders in the world). The researchers isolated various active peptides from the venom. Each peptide was studied to see how it would affect specific pain targets known as ion channels, which transmit pain signals through the body.

About 40 per cent of the tested spider species contained at least one peptide that blocked pain channels. The researchers plan to conduct animal studies to test the peptides’ clinical potential, looking for any unforeseen side effects, whether the substances break down in the body and other outcomes, Dr. Smith said.

“We’ve got a massive library of different venoms from different spider species and we’re branching out into other arachnids: scorpions, centipedes and even assassin bugs,” Dr. Smith said.

Some, such as the Sydney funnel-web spider, a native to Australia, were easy to milk because they are very aggressive. “Literally, you have to just look at them and they’ll start dripping venom from their fangs,” Dr. Smith said. The spider’s venom, however, didn’t contain ingredients capable of blocking pain channels, she said.

Others, including South American tarantulas the size of dinner plates, had to be anesthetized and the muscles around the venom gland stimulated for venom to be produced, she said. A university researcher traveled the world to collect venoms from spiders kept by arachnid enthusiasts and pet shops.

Australia is a natural fit for this research, Dr. Smith said. “We have a plethora of really good venomous animals: You name it we’ve got it, pretty much. Australia is the venom land.”

The Australian research is funded in part by Janssen Pharmaceuticals Inc., a unit of Johnson & Johnson. “We think this is scientifically promising, but it is too early to put time frames around when this might be in the clinic or a product would be available,” a Janssen spokesman said.

Experiments with the black mamba snake also aim to develop nonaddictive painkillers. The snake, which has olive-gray skin and can grow as long as 12 feet, gets its name from the color inside its mouth, which it displays when threatened.

Researchers at France’s National Center for Scientific Research tested peptides from the black mamba snake’s venom called mambalgins on mice and found potent painkilling properties. The peptides focused on a different pain pathway than the opioid receptors targeted by morphine, according to the research, published in the journal Nature in 2012.

Venom from the sun anemone is being developed into a drug called dalazatide by Seattle-based biotech company Kineta Inc. A human clinical trial with the drug as a treatment for psoriasis recently concluded and results are expected to be released in the next few weeks, according to Kineta. Unlike traditional treatments for autoimmune disorders that suppress the entire immune system, Kineta’s drug is intended to block only the white blood cells that cause the diseases, said company chief executive Charles Magness.

Source: The Wall Street Journal Copyright ©2015 Dow Jones & Company, Inc (21/04/15)

Athlete's foot cream 'could repair nerve damage' (21/04/15)
A common athlete’s foot cream sold over the counter at most chemists could help people living with multiple sclerosis, a new study claims.

Researchers believe the drug miconazole - the active ingredient in Daktarin - instructs stem cells in the brain to repair nerve damage. The discovery comes after a team at Case Western Reserve University in Ohio tested more than 700 drugs to see if anyone would be useful against MS.

The athlete’s foot drug and a cream used to treat eczema were found to stimulate the regeneration of damaged brain cells. It was found to reverse paralysis in mice.

"We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now we had no way to direct them to act," said Dr Paul Tesar, Professor of Innovative Therapeutics at Case Western Reserve School of Medicine.

"Our approach was to find drugs that could catalyse the body's own stem cells to replace the cells lost in multiple sclerosis."

The team said that much work remains before multiple sclerosis patients might benefit from the promising approach.

Scientists still must find ways to transform the medications for internal use and determine their long-term efficacy and potential side effects.

However they said the initial findings show promise and the drugs have been shown to work on human stem cells.

“This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients,” said Dr Robert Miller of the neurosciences faculty.

"The drugs we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system. It showed a striking reversal of disease severity in the mice.”

The research was published in the journal Nature.

Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (21/04/15)

Extending natalizumab up to eight weeks ‘safe and effective’ (21/04/15)
In a study of 1,964 patients with multiple sclerosis, researchers at the NYU Langone Multiple Sclerosis Comprehensive Care Center found that extending the dose of natalizumab from four weeks up to eight weeks was shown to be well-tolerated and effective in patients, and resulted in no cases of the potentially fatal side effect progressive multifocal leukoencephalopathy (PML).

The drug showed similar efficacy in treating disease activity among patients, according to the study led by Lana Zhovtis-Ryerson, MD, an assistant professor of neurology at the NYU Langone Multiple Sclerosis Comprehensive Care Center.

Natalizumab is an infusion drug known as a monoclonal antibody that is used to prevent MS symptoms and flare-ups and slow worsening disability.

However, taking the medication for longer than two years may increase risk for a rare but potentially fatal side effect called PML, an untreatable brain infection that occurs in up to 1.3 percent of patients taking natalizumab.

The medication is typically prescribed in 300-milligram infusions every four weeks.

"There remains much unknown about whether the drug will lose effectiveness if dosing is extended," explains Dr. Zhovtis-Ryerson. "Our study showed treatment with natalizumab was safe for patients with similar efficacy reported as the standard dosing, potentially enabling patients to stay on effective MS medication at a reduced frequency of infusions and with lower risk of PML. "

Zhotvis-Ryerson and colleagues at 10 American MS. Centers sought to compare the safety and efficacy of an extended dose of natalizumab to the standard dose. They retrospectively compared 1,078 patients taking a standard 4-week dose to 886 taking an extended dose between 4 weeks, 3 days and 8 weeks, 5 days.

The researchers found extending the dosing schedule of natalizumab to between 5 and 8 weeks does not affect the drug's efficacy profile with 65 per cent of participants in each group not showing clinical MS activity, and comparable rates of new lesions reported on imaging. Zero cases of PML were reported in the extended dosing group, while two cases were reported in the standard dose group, though the researchers said statistical significance has not been reached yet. No other major adverse events were reported.

"While the findings are encouraging, more research is needed to determine whether extending natalizumab dosing may reduce disability progression," says Dr. Zhovtis-Ryerson.

Natalizumab is manufactured by Biogen and Elan, and sold under the name Tysabri.

Source: MedicalXpress © Medical Xpress 2011-2015, Science X network (21/04/15)

Doctors urged to consider diverse symptoms (20/04/15)
Medical professionals have been urged to consider a wide range of possible symptoms when it comes to neurological conditions such as multiple sclerosis.

The move comes after a case where a seven-year-old boy's only symptoms were abdominal pains.

According to the study 'Acute Abdominal Pain As The Only Symptom Of A Thoracic Demyelinating Lesion In Multiple Sclerosis', published in the journal Brain And Development, the child had a new demyelinating lesion that showed up on his spine.

The boy had his first MS symptom at the age of three. At that time, he had spastic gait and was treated with intravenous methylprednisolone (m-PSL). Although he continued to have slight spasticity in both his ankle joints, his symptoms were greatly improved.

Later, at the age of six, the boy had a second MS symptom. He appeared at the doctor due to neck and upper extremity pain and was diagnosed with multiple sclerosis. A more aggressive means of treatment included interferon-beta 1a (IFN β 1a) and plasmapheresis in addition to m-PSL. Treatment with IFN β 1a was stopped because the boy had frequent episodes of vomiting and poor eating, both of which cleared up one month after stopping IFN β 1a treatment.

With the newest relapse, the boy was treated again with m-PSL and IFN β 1b (rather than IFN β 1a). Remarkably, there was a reduction in the demyelinating lesion with the end of treatment, as well as a resolution of symptoms after three weeks.

“This case is remarkable in that the only symptom of a longitudinally extensive, thoracic, demyelinating lesion was abdominal pain,” said Dr. Shohei Nomura, lead author of the case study.

“Though it is unclear why the only manifestation of this patient’s extensive thoracic lesion was abdominal pain, this case supports the notion that the size and localization of demyelinating lesions might not directly correspond to the symptoms observed. Therefore, clinicians must be careful to consider neurogenic sources of diverse symptoms, especially those related to autonomic dysfunction, in demyelinating diseases such as multiple sclerosis.”

Source: Multiple Sclerosis News Today © BioNews Services 2015 (20/04/15)

Generic version of MS drug gets FDA approval (17/04/15)
The Food and Drug Administration has approved the first-ever generic version of the multiple sclerosis drug, Copaxone, which was developed by Momenta Pharmaceuticals. However, it’s still unclear when the drug might become available to patients.

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

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

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

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

Study suggests wearables could help MS patients (15/04/15)
A three-week study by Biogen and the American patient network PatientsLikeMe claims to have found patients with multiple sclerosis can benefit from a wearable device that tracks their activity, reports the Boston Business Journal.

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

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

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

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

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

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

New drug could reverse MS damage (15/04/15)
A new experimental drug, anti-LINGO-1, has been found to repair myelin and so radically improving nerve signalling, reports The Daily Telegraph.

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

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

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

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

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

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

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

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

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

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

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

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

Beta-interferons ‘not associated with delayed onset of SPMS’ (13/04/15)
A Canadian study has found no link between the delayed onset of secondary progressive multiple sclerosis and treatment with beta-interferons.

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

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

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

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

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

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

Beta-interferons ‘not associated with delayed onset of SPMS’ (13/04/15)
A Canadian study has found no link between the delayed onset of secondary progressive multiple sclerosis and treatment with beta-interferons.

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

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

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

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

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

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

PML death linked to Tecfidera (10/04/15)
The brain infection progressive multifocal leukoencephalopathy (PML) has killed a Dutch psoriasis patient who was taking a high dose of a drug with ingredients similar to Tecfidera. Tecfidera is used for multiple sclerosis, which the Dutch patient didn’t have, and the medicine was made in a compounding pharmacy and not by Biogen. Yet, according to, doctors claim the case suggests the infection could emerge in people who aren’t showing warning signs.

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

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

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

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

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

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

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

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

Progressive MS treatment phase III study update (07/04/15)
MedDay, a biotechnology company focused on the treatment of nervous system disorders, has provided further information about the design of its pivotal clinical trial (MS-SPI) to investigate the efficacy and safety of MD1003 in the treatment of primary and secondary progressive multiple sclerosis.

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

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

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

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

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

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

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

Patients could benefit from brain boost (07/04/15)
Multiple sclerosis patients could one day benefit from treatments that boost their brain function, a study has suggested.

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

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

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

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

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

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

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

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

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

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

Immune system component found to be related to MS neurodegeneration (07/04/15)
A study published in PLOS ONE provides new insights into the relationship between the immune system and neurodegeneration and clinical disability in MS, reports Multiple Sclerosis News Today.

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

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

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

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

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

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

MS patients less susceptible to gout claims study (07/04/15)
A group of researchers have been investigating the theory that high levels of uric acid, whch may have protective effects on neurons and are present in gout patients, could mean gout resulting in a reduced risk of developing neurological disease, reports Multiple Sclerosis News Today.

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

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

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

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

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

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

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

Statins therapy yields conflicting results (02/04/15)
Researchers at the IRCCS Centro Neurolesi “Bonino-Pulejo” and the University of Messina in Italy have performed a review on the immunomodulatory activity reported for statins in the treatment of multiple sclerosis (MS) and on clinical trial results, reports Multiple Sclerosis News Today.

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

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

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

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

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

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

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

Phase 1 trial completed (01/04/15)
Vaccinex, Inc. has today announced the successful completion of a multicenter phase 1, randomized, double-blind, placebo-controlled, single ascending-dose safety and tolerability study in adult patients with multiple sclerosis.

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

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

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

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

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

Clues to 'brain fog' in chronic fatigue patients found in spinal fluid (01/04/15)
People with chronic fatigue syndrome show a distinct pattern of immune system proteins in their spinal fluid, reports HealthDay - a finding that according to researchers could shed light on the "brain fog" that marks the condition.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

MS drug 'may already be out there' (01/04/15)
Depression and heart-disease drugs are to be tested in a trial to find treatments for multiple sclerosis from existing medicines, reports the BBC.

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

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

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

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

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

Amiloride - licensed to treat heart disease

Fluoxetine - used in depression

Riluzole - for Motor Neurone Disease

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

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

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

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

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

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

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

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

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

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

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