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Emerging Therapies, Progressive MS, Wellness/Lifestyle and Other Research News from ECTRIMS Meeting

October 21, 2015

  • Results from clinical trials in new approaches to treating progressive and relapsing MS, wellness and lifestyle research, and myelin repair strategies took center stage during the European Committee for Treatment and Research in MS (ECTRIMS) meeting held in Barcelona, Spain in early October.
  • More than 9,000 participants convened to share progress in understanding and treating MS.
  • Read blogs from the meeting
  • Explore scientific summaries (abstracts) on the ECTRIMS Website. Search specific topics of interest or sessions 

Below are a few highlights of presentations focusing on stopping MS, restoring function, and ending MS forever. In most cases, studies presented are considered preliminary. Many will be analyzed more thoroughly, and likely published in peer-reviewed medical journals. Confidence in a study’s findings is reinforced when it is repeated by others, who attain similar results.

Stopping MS - Therapies

Many studies presented showed the continued benefit and safety of available therapies, as well as more evidence that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying accumulation of disability and protecting quality of life. A new MS Brain Health initiative is promoting the message of minimizing delays in the diagnosis and time to treatment to reduce the risks of MS progression.

Ocrelizumab in Primary Progressive MS: Ocrelizumab is a monoclonal antibody that targets a specific population of immune B cells. B cells make proteins that help fight infections and are thought to also play a role in the immune-mediated damage that leads to MS. Results were presented of a clinical trial of ocrelizumab in 732 people with primary progressive MS. Participants were given either ocrelizumab or inactive placebo by in-vein infusions about every 6 months. Compared to placebo, ocrelizumab significantly reduced the risk of progression of clinical disability (according to the standard EDSS scale) by 24%, and had other positive outcomes. The main side effects were reactions to the infusions, and a slight increase in the risk for infection. A more complete safety analysis is ongoing. (Abstract 228) Read more

Ocrelizumab in Relapsing MS: Results from two phase III trials of ocrelizumab in relapsing MS were positive compared to Rebif®(interferon beta-1a, EMD Serono and Pfizer). Ocrelizumab reduced the risk of relapse by 46 to 47% compared to Rebif, reduced the risk of disease progression by 40%, and had other positive outcomes. The main side effects were reactions to the infusions, and a slight increase in infections. (Abstract 190) The sponsor, Genentech (a member of the Roche Group) stated that it plans to apply for marketing approval from the FDA in early 2016.

Minocycline Before MS Diagnosis (CIS): Dr. Luanne Metz (University of Calgary) reported on a Phase III trial of a relatively inexpensive oral antibiotic called minocycline, which is often prescribed to treat acne. In addition to its bacteria-killing action, it reduces inflammation. The trial tested minocycline against placebo in 144 people who had clinically isolated syndrome. Results showed that over 6 months, those taking twice daily minocycline had a 44.6% reduced risk of developing definite MS, compared to those taking placebo. There were no unexpected side effects outside of the most common that occur with this antibiotic, which carries several warnings including that it is not to be taken during pregnancy. (Abstract 227)

5-Year Results from Lemtrada: Reports from two ongoing extension studies of alemtuzumab (Lemtrada,® Genzyme, a Sanofi company), approved for relapsing MS, suggest this therapy continued to show effectiveness against relapses and brain volume loss after 5 years in people who had participated in the CARE 1 and CARE 2 trials, many of whom only received two courses of yearly infusions. Adverse events that have been well documented in the medication guide (.pdf) were reported to be comparable or reduced during the extension period compared with the original studies. (Abstracts 151, 152)

Lectures Focus on Progressive MS and Treatment Strategies: Giving the Keynote address, Professor Alan J. Thompson (University College London) focused on knowledge gaps and advances in research on progressive MS, which impacts more than half of all the people who have MS. He highlighted the work of the International Progressive MS Alliance as a force that is already driving research forward. Professor Giancarlo Comi (University Vita-Salute San Raffaele, Milan) gave the Charcot Award Lecture focusing on emerging approaches to treating MS. He focused on the need for evidence that will enable a personalized medicine approach, based on disease characteristics and predictive markers that would determine the best treatment course for an individual. He emphasized the importance of early treatment for better outcomes, stating his personal belief that there will be a shift toward the idea of “induction therapy” – hitting the disease hard and early.

Restoring Function: Nervous System Repair

Thyroid-Like Hormone for Repair? Dr. Dennis Bourdette (Oregon Health and Science University) sped up myelin repair in mice using an experimental drug called sobetirome. This is a thyroid-like hormone that is already in clinical trials for lowering cholesterol. We know that the thyroid hormone boosts the capabilities of myelin-making cells, but is not viable to treat MS because of adverse effects on heart, bone, and muscle. Sorbetirome may work without these side effects; the National MS Society is funding this team to explore this option in MS models. Since it is already in clinical trials for another indication, demonstrating safety and effectiveness in MS may take less time than usual. (Abstract P583)

Myelin and Nerve Repair? Dr. Bernard Mueller and colleagues (AbbVie Inc.) reported their findings on the experimental therapy ABT-555, which is an antibody to a signaling molecule in the nervous system. When ABT-555 was administered to mice with an MS-like disease, the mice recovered from disease, and experienced both myelin repair and nerve fiber regeneration within spinal cord lesions. Early tests of ABT-555 are underway in healthy volunteers and in people with MS. (Abstract P582)

Network Testing Mesenchymal Stem Cells (MSC): MSC’s are “spare parts” that are being explored for their potential to improve the body’s ability to repair damage to nervous system caused by MS. A roadblock to research has been that teams use different treatment protocols, making it hard to compare results. Now a collaborative trial may overcome this problem. “MESEMS” is a network of trials all following the same protocol and sending their data and MRI scans to centralized locations for comprehensive analysis. This way they can increase the number of participants and get more powerful results. They plan to enroll 160 people across Europe and Canada, and will be recruiting people with all forms of MS as long as they show signs of active disease or inflammation. (Abstract P1087)

More Anti-LINGO Results: Last spring promising results were reported from a phase 2 clinical trial of the myelin repair strategy called anti-LINGO (Biogen). The study involved IV infusions or placebo every 4 weeks for 20 weeks to 82 people who had a first episode of optic neuritis. Those who had been given anti-LINGO had faster nerve signals along the optic nerve of the affected eye, compared to those on placebo. Now Biogen researchers reported that in a sub-study involving 39 participants, those on anti-LINGO also had reduced loss of nerve signal strength in the unaffected eye, compared to placebo.  This suggests that anti-LINGO may have additional benefits in optic neuritis than previously reported. The therapy seemed to be well tolerated except for some infusion reactions. Another phase 2 trial is ongoing in people with relapsing MS. (Abstract 231)

Restoring Function: Wellness, Lifestyle, Symptoms

Approaches to Diet: The idea of intermittent fasting as a way to fight inflammation is being explored by MS researchers, but this kind of diet can be hard to stick with. A small trial involving 48 people with relapsing-remitting MS was performed by Dr. Markus Bock and colleagues (Universitätsmedizin Berlin) took a different approach. The investigators studied various diets that may affect “ketone bodies” – molecules in the liver that may protect the brain and spinal cord. Compared to participants who just followed their usual diets, participants who followed either a “ketogenic diet” (a high-fat, adequate-protein, low-carbohydrate diet) or a prolonged-fasting diet (an initial 7-day fast followed by a Mediterranean diet) reported improved quality of life and had improved cholesterol levels. Larger studies are needed to fully explore the potential benefits of these approaches. (Abstract P1509)

Gut Microbiome Offers Clue to Potential Treatment: Dr. Aiden Haghikia (Ruhr-University Bochum, Germany) and colleagues previously found in mice that gut bacteria giving off short-chain (verses medium or long-chain) fatty acids could protect against the development of MS-like attacks. To translate these results to humans, the team administered daily capsules of “proprionate,” which contains short-chain fatty acids, to 18 healthy volunteers. They found no side effects, and also found that cells that activate immune attacks in MS were suppressed. They also reported that other cells, called Tregs, which can turn off attacks, increased by 25-30%. This early report shows the potential of a nutritional supplement that could be tested for its benefits in people with MS. (Abstract 230)

Online Fatigue Program: Dr. Jana Poettgen (University Medical Center Hamburg, Germany) and colleagues conducted an international clinical trial to see whether an online fatigue management program involving a cognitive-behavioral approach could reduce fatigue in people with all forms of MS. Participants were randomly assigned to a home-based, 3-month online program or to a wait-list control group. The team reported that the program reduced fatigue and anxiety, but did not improve depression. This type of program may hold promise for providing programs to people with MS who don’t have local access to programs, or find it difficult to travel. (Abstract 135)

Make a Muscle: A team from Denmark and Belgium led by Dr. Ulrik Dalgas (Aarhus University) noted that people with MS tend to lose muscle mass and that they have fewer “myogenic stem cells” – cells in the body that help rebuild muscle. The team reported that after a 12-week, high-intensity training program (involving exercise machines for strengthening upper and lower body muscles), myogenic stem cells increased by 165% in people with MS. This kind of exercise program may not be for everyone affected by MS, but it’s encouraging to know that such regrowth is possible. (Abstract P813)

Biology of Depression in MS: Dr. Nancy Sicotte (Cedars-Sinai Medical Center, Los Angeles) and an international team used brain imaging to examine the biological basis of major depressive disorder in people with and without MS. Previous research suggests that depression is common in people with MS and can occur in association with cognitive impairment, and these problems have been linked to shrinkage of the hippocampus, a part of the brain involved in memory. In this study, the investigators found that people with MS and depression had more cognitive impairment and hippocampal shrinkage, than those with non-MS depression. However, those with MS depression also shared some features with those who have non-MS depression, suggesting that there may be some similarities between major depression in MS and non-MS depression, with possibly different biological underpinnings. More analysis of this study is ongoing. (Abstract 98)

Sleep and Fatigue: Some studies suggest that as many as half of those with MS experience sleep-related problems. Several presentations focused on sleep issues, including one by Dr. Mark Gutesblatt (South Shore Neurologic Associates, Patchogue, NY) whose team looked at cases involving 206 people with MS who experienced fatigue and had undergone overnight sleep studies. They found that moderate to severe sleep disordered breathing (a range of sleep-related breathing problems including apnea) was more common during REM sleep than during non-REM sleep. Some (12%) never achieved REM sleep, which is thought to be the most restorative stage of sleep, underscoring the importance of treating sleep disorders in MS. (Abstract EP1270)

Can Exercise Change Brain Function? Yes, according to several presentations. Dr. Francesca Tona (Sapienza University, Rome) and colleagues looked first at whether 26 people with MS with balance problems would benefit from home-based training using videogames and the Wii balance board. They used the board and games five times a week for 30-minute sessions over 12 weeks. Many experienced improvements in their balance after the program. Next, the researchers explored how “functional connectivity” – the connections between different areas of the brain measured using neuroimaging – changed after the 12 weeks, compared to before engaging in the program. They found increased connectivity in several areas of the brain including the cerebellum which controls bodily movement, providing evidence of neuroplasticity that improved function. This was especially strong in people who had benefited most from the program. (Abstract 183)

Cognitive Rehab Rewiring the Brain: Along the same lines, Dr. Arman Eshaghi (UCL Institute of Neurology, London) and colleagues in Iran and the U.K. looked at how cognitive rehabilitation may rewire the functional connectivity of brain circuitry in 27 people with MS. Participants were given repeated computer-based verbal and visual memory tasks twice weekly for 3 months, alternated with 3 months of no intervention. They were given various memory tests, some while undergoing functional MRI brain imaging to observe the brain in action. The researchers found that the cognitive rehab program improved memory test scores as well as functional connectivity in specific areas of the brain. The researchers plan to see whether they can identify brain circuitry characteristics to identify people most likely to benefit from this type of rehabilitation. (Abstract 99)

Improving Memory: A team from Italy and the United Kingdom, led by Dr. Micaela Mitolo (IRCCS San Camillo Hospital, Venice), tested an intensive program designed to target multiple areas of the brain and thus multiple cognitive problems. Among the 15 people who underwent 1-hour rehab sessions for 5 days a week for 4 weeks, cognitive function improved, even in areas not specifically involved in the training. Brain imaging also showed that compared to the participants who did not undergo the program, those who did experienced increased functional connectivity. (Abstract 180)

Rebif is a registered trademark of EMD Serono and Pfizer.
Lemtrada is a registered trademark of Genzyme, a Sanofi company

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.


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