Novel Molecule May be Used to Track and Treat MS

Scientists at Purdue used a novel approach to show that a molecule called acrolein is elevated in blood and urine from mice with MS-like disease and from people with MS, compared to those without the disease. Acrolein is normally a waste product, but seems to accumulate in people with neurologic disease, becoming toxic to nerve cells. They are now testing whether acrolein levels correlate with disease activity, to determine if this molecule may eventually be used to identify MS with a simple blood test. Medications targeting acrolein are already on the market, raising its potential as a therapeutic target for MS.

Read more in Purdue University News

Read the paper in Frontiers in Neurology

New MS Research

Research on immune activity in MS

Understanding and stopping MS in its tracks requires a better understanding of the role that the immune system plays in this disease. This system is involved both in the inflammatory attacks on myelin and, very possibly, in the injury to axons (the wire-like nerve fibers) that contributes to longer-term disability. Research on the immune system includes studies on:

• Understanding components of the immune system such as T cells, B cells, and antibodies
• Identifying new targets for therapeutic intervention while leaving the rest of the immune system capable of fighting infections
• Identifying substances and processes involved in the injury of axons
• Identifying the body’s natural immune messenger molecules that can either turn on or turn off immune attacks

Significant progress is being made in understanding the immune system's involvement in MS, which will help drive breakthrough solutions to change the world for everyone with MS.

We’re making progress

Studies of the immune system in MS laid the groundwork for every disease-modifying therapy now available, and these studies continue to hold promise for finding ways to stop MS. Here are reports of recent progress:

Researchers co-funded by the National MS Society report study results indicating that “Tregs” – regulatory immune cells that are known to be dysfunctional in people with MS – play a role in promoting formation of new myelin following damage. If the results are confirmed through further research, these basic laboratory studies could eventually be translated to promising new therapeutic approaches to stimulating myelin repair to restore function in people with MS. Read more

Treatment with ATX-MS-1467 (Apitope) – an injected immune therapy whose early development was supported by the National MS Society through Fast Forward, the Society’s commercial research funding program – was reported to reduce disease activity on MRI scans in two small open-label studies involving people with relapsing MS. This is an approach to identify pieces of human proteins, called “peptides,” that might be able to reinstate “immune tolerance” – in effect, train immune cells to ignore myelin – to suppress MS attacks. Read more

Scientists at the University of Florida, funded in part by the National MS Society, took a novel approach to turn off immune attacks in mice with an MS-like disease. The team used a harmless virus to deliver a gene coding for a specific component of myelin, a key target of immune attacks in MS. Further research is needed to verify and refine this approach before it can be tested in people. Read more

Results Published from Trial of Siponimod in Secondary Progressive MS

• Results of a 60-month, phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS have been published. The results were originally presented in September 2016 at the ECTRIMS conference.
• The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23% lower average change in brain volume and reduced lesion volume. There was no significant difference seen between groups in the timed 25-foot walk.
• The therapy was generally well tolerated and similar to adverse events reported for similar compounds. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.
• Dr. Ludwig Kappos (University of Basel in Switzerland) and a large team of investigators report detailed results of the trial in The Lancet (online March 22, 2018). A commentary about the results by Drs. Luanne Metz and Wei-Qiau Liu (University of Calgary) is also published online.

DETAILS
Background: Siponimod (BAF312) is an experimental immune system-modulating therapy that was designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya® (fingolimod, Novartis International AG). Gilenya, was approved in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug;12(8):756-67).

Siponimod is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Siponimod also distributes effectively to the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects.

The Study: Participants with secondary progressive MS were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale that was sustained for at least 3 months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/tolerability.

Results: The results were originally presented in September 2016 at the ECTRIMS conference. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had a 23% lower average change in brain volume, and reduced MRI-detected brain lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

Safety: The therapy was generally well tolerated and similar to adverse events reported for related compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections. More of those taking siponimod than the placebo experienced adverse events (89% vs 82% patients), such as a slower heart rate, high blood pressure, reduced white blood cell counts, macular oedema (swelling at the back of the eye), increased liver enzymes, and increased numbers of convulsions.

Dr. Ludwig Kappos (University of Basel in Switzerland) and a large team of investigators report detailed results of the trial in The Lancet (online March 22, 2018). A commentary about the results by Drs. Luanne Metz and Wei-Qiau Liu (University of Calgary) is also published online.

Comment: “While the magnitude of this response is somewhat modest, it represents a milestone in our unrelenting search for treatments that will benefit people living with progressive forms of MS,” said Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society.

Resources
Read about secondary progressive MS
Read about the International Progressive MS Alliance, an unprecedented global collaboration of MS organizations, researchers, clinicians, pharmaceutical companies, and people with progressive MS, transforming the landscape of multiple sclerosis.

 

Zinbryta (daclizumab), a Therapy for Relapsing MS, is Withdrawn from Market

• Biogen and AbbVie have announced the voluntary withdrawal Zinbryta ™ (daclizumab) from the worldwide market.
• Zinbryta is an immune-modulating therapy that was approved in 2016 for people with relapsing MS and generally reserved for people who had an inadequate response to two or more MS therapies.
• According to a company press release, the European Medicines Agency had raised new safety concerns related to reports of inflammation of the brain or its surrounding tissues (inflammatory encephalitis and meningoencephalitis) among people taking Zinbryta.
• Individuals currently taking Zinbryta should contact their healthcare providers to determine alternative treatment options, and to continue safety monitoring. According to the medication guide, this would include monthly blood tests to monitor liver function for up to six months after the last dose.

Best MS Books (29 books)

29 books based on 16 votes: Break The Spell by A.M. Bostwick, Mom's Story, A Child Learns About MS by Mary Jo Nickum, Multiple Sclerosis: The Questions Y...

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Results Announced from Phase 2 Clinical Trial of Ibudilast Suggest Reduction of Brain Atrophy (Shrinkage) in People with Progressive MS

SUMMARY

• Top-line results were announced of a phase 2 clinical trial testing an oral anti-inflammatory therapy ibudilast (MN-166, MediciNova, Inc.) in people with progressive forms of MS.
• The results announced in a press release concluded that ibudilast was well tolerated and significantly slowed the rate of brain atrophy compared to placebo. Brain atrophy (shrinkage) has been linked to cognitive and physical disability in MS.
• The trial was conducted at the Cleveland Clinic and 27 other sites across the U.S., and involved 255 people with primary or secondary progressive MS.
• The study was principally funded by NeuroNEXT Network, a clinical trials initiative of the National Institutes of Health, with additional support by MediciNova, the company that supplied ibudilast. The National MS Society also provided funding support.
• Further details are schedule to be presented Saturday, October 28^th at the MSParis2017 – 7th Joint ECTRIMS-ACTRIMS Meeting.
• These phase 2 results may lead the way to the testing of ibudilast in larger phase 3 trial(s), which would be needed before the company could apply for marketing approval from the FDA, the European Medicines Agency or other regulatory agencies. Ibudilast was designated by the FDA as a “Fast Track Product” which could speed its future development as a possible treatment of progressive MS.

“These results sound like a very promising step toward a potential new therapy for people with progressive forms of MS, for whom there are few treatment options,” said Dr. Bruce Bebo, Executive Vice President, Research, National MS Society.

DETAILS
Background: Ibudilast (MN-166, MediciNova, Inc.) inhibits an enzyme called phosphodiesterase, resulting in suppression of inflammation. While considered a “New Molecular Entity” in the United States and Europe, ibudilast is marketed in Japan and Korea to treat cerebrovascular disorders and asthma. It is being also being investigated in the U.S. for its potential to treat ALS and drug addiction.

The study was principally funded by NeuroNEXT Network, a clinical trials initiative of the National Institutes of Health, with additional support by MediciNova, the company that will supply ibudilast. The National MS Society also provided funding support because of its focus on progressive MS and because the trial’s design may answer important questions about the best ways to measure the benefits of therapies aimed at protecting the nervous system from MS.

The study: The trial, known as “SPRINT-MS,” was led by Principal Investigator Robert Fox, M.D., M.S., FAAN, Staff Neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic. It was conducted at the Cleveland Clinic and 27 other sites across the U.S. The trial involved 255 people with primary or secondary progressive MS. The primary outcome measure was change in brain atrophy (as measured by an MRI analysis technique called brain parenchymal fraction) after 96 weeks.  Brain atrophy (shrinkage) has been linked to cognitive and physical disability in MS. Other imaging, safety, clinical and quality of life outcomes were also measured.

The results announced in a press release from MediciNova concluded that ibudilast was well tolerated and significantly slowed the rate of brain atrophy compared to placebo. Further details are schedule to be presented on Saturday, October 28^th at the MSParis2017 – 7th Joint ECTRIMS-ACTRIMS Meeting.

What’s Next? These phase 2 results may lead the way to the testing of ibudilast in larger phase 3 trial(s), which would be needed before the company could apply for marketing approval from the FDA, the European Medicines Agency or other regulatory agencies. Ibudilast was designated by the U.S. Food and Drug Administration as a “Fast Track Product” which could speed its future development as a possible treatment of progressive MS.

Study Strengthens Link Between Low Vitamin D Levels and Risk of MS

SUMMARY

• A study based on stored blood samples of 800,000 pregnant Finnish women found that vitamin D levels might predict who is at risk for later developing MS.
• Vitamin D blood levels of 1,092 women later diagnosed with MS were compared to those of 2,123 women around the same age and region who did not develop the disease.
• Women who developed MS later had average D levels lower than the women who didn’t.
• More research is needed on how to best supplement vitamin D and to know whether and who it might help. Read more more about Vitamin D and MS.
• The study was published on September 13, 2017 in Neurology.

DETAILS
Background: Researchers believe that several genetic and environmental factors influence whether a person will get MS. These factors may also impact the severity of the disease. Scientists are eager to find risk factors for MS that can be modified to possibly prevent MS and reduce disease activity. Research is increasingly pointing to reduced levels of vitamin D in the blood as a risk factor for developing MS, and studies are underway to determine if vitamin D levels influence MS disease activity.

This Study: This study -- the largest such study to date – took advantage of a unique resource: stored blood samples from 800,000 Finnish women who had undergone routine prenatal testing during pregnancy. The study was designed to determine whether and to what extent vitamin D deficiency is associated with future risk of developing MS. The team identified 1,092 of the women who were later diagnosed with MS. The researchers compared their vitamin D levels to those of 2,123 women who were about the same age and lived in the same area but did not develop MS. Of those women whose medical records were available for examination, an average of 9.5 years had lapsed between the time of the first blood sample and the date of an MS diagnosis. For this study, classifications of blood levels of vitamin D (25-hydroxyvitamin D) included “deficient” (less than 30 nmol/L) and “adequate” (greater than or equal to 50 nmol/L).

Results: The team found that overall as vitamin D levels increased, the risk of later developing MS decreased. Women with the greatest deficiency in vitamin D had a twofold increase in the risk of developing MS, and those with the highest vitamin D levels had the lowest risk of a later MS diagnosis. Most of the women in the study were considered to have deficient or insufficient levels of vitamin D. Of the women who developed MS, 58 percent had deficient levels of vitamin D, compared to 52 percent of the women who did not develop the disease.

The researchers conclude that the results directly support vitamin D deficiency as a risk factor for MS and that correcting this among reproductive age women may reduce their future risk of developing MS. In addition, a previous study of this same group of women found that maternal vitamin D deficiency during pregnancy doubled the risk of MS in their offspring, and a Danish study found that low vitamin D levels in infants was associated with an increased MS risk in adulthood, suggesting that improving a woman’s vitamin D levels during pregnancy may also reduce the risk of MS in her children.

The study, by a team including Drs. Kassandra Munger and Alberto Ascherio (Harvard T. H. Chan School of Public Health in Boston), was published on September 13, 2017 in Neurology.

Comment: This largest study of its kind to date adds to growing evidence that low levels of vitamin D increase the likelihood of developing MS. Since this study included only women, who were mostly white, the results may not apply to men or to other racial groups. It also did not account for other potential risk factors that may have played a role.

An editorial in the same issue of Neurology by Drs. Ruth Ann Marrie Christopher Beck addresses the question of whether there is enough evidence now to make sweeping recommendations on vitamin D supplementation. They note, “Vitamin D supplementation is a simple intervention that would be highly cost-effective even if it prevents only a proportion of MS cases...,” concluding, “It is time to take an active approach to preventing MS, at a minimum targeting those individuals with an elevated risk of MS, including smokers, the obese, and those with a family history of MS.”  Read more more about Vitamin D and MS