The accelerated pace of MS research was on full display at the recent ECTRIMS (European Committee for Treatment and Research in MS) meeting in Barcelona, Spain – the world’s largest gathering of MS researchers. Over 9,000 investigators convened in October to share breaking news and progress towards stopping MS, restoring lost function and ending MS forever. Below you’ll find a few of the highlights.
Ocrelizumab in Primary Progressive MS
Making the most “buzz” were results presented on a clinical trial by Genentech (a member of the Roche Group) involving 732 people with primary progressive MS treated with the monoclonal antibody ocrelizumab. Ocrelizumab targets a protein that appears on immune B cells during specific stages of their life cycle. B cells make antibodies to help fight infection and perform other functions to stimulate the immune system. Results showed that compared to placebo, ocrelizumab modestly reduced the risk of progression and had other positive outcomes. This is the first large-scale clinical trial to show positive results in people with primary progressive MS. We don't yet know what mechanism might be driving these results in progressive MS, so we are eager to see more information when these results are published.
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. 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
Dr. Luanne Metz (University of Calgary) reported on a Phase III trial of an 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.
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 Society is funding this team to explore this option in MS animal models. Since it is already in clinical trials for another indication, demonstrating safety and effectiveness in MS may take less time than usual.
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.
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.
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 sustain.. 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.
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 suggests that after testing in humans, a nutritional supplement may be found to have benefits in people with MS.
Exercise Improves Brain Function
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.
High Intensity Exercise Stimulates Muscle-Building Cells
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.
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.