Nervous System Repair – Multiple Strategies in the Pipeline

Nervous system repair is getting a lot of attention this week in Barcelona at ECTRIMS, the European Committee for Treatment and Research in MS, where 9,000 experts in MS have gathered to share research ideas and results. When I was working in the lab as a neuroscientist not so many years ago, the idea of a therapy with the capability to repair the nervous system seemed very far away. Today, we have a better understanding of factors that control the body’s natural repair mechanisms, and closer than ever to potential repair therapies.

In fact, there are several experimental strategies actually in clinical trials right now.  Repair trials underway include a trial testing clemastine, an oral antihistamine used to treat allergy symptoms; an antibody called rHIgM22, which was well tolerated in one study in people with all types of MS; and a monoclonal antibody called anti-LINGO that also has shown positive results in a phase 2 study in people with a first episode of optic neuritis.

In order to reach our ultimate goal of repairing the damaged nervous system and restoring function for people with MS, we need more of these strategies in the pipeline. So it’s been encouraging to see some of the new approaches being discussed at ECTRIMS.

Prof. Dennis Bourdette and his team (Oregon Health and Science University) sped up myelin repair in mice using an experimental drug called sobetirome. This agent is a thyroid-like hormone that mimics its biological effects and is already in clinical trials for lowering cholesterol. We know that the thyroid hormone boosts the capabilities of myelin-making cells, but is not a viable therapeutic option for people with MS, due to adverse effects on heart, bone, and muscle. Sorbetirome may work effectively 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 may take less time usual. (Abstract P583)

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. The company notes some exciting findings as a result of an early study of this experimental antibody that is underway in healthy volunteers and in people with MS. (Abstract P582)

Some strategies involve improving the “micro” environment in the brain to enable repair, rather than administering a specific therapy. Prof. V. Wee Yong’s team (University of Calgary) is studying microglia, which are brain cells that mimic immune cells known as macrophages. These cells can be either damaging or repairing, depending on the cell subset involved. This group is attempting different strategies to promote the type that does repair. They report that an exercise activity can boost the repair-friendly environment in mouse models of myelin damage. (Abstract 201) Understanding what leads to repair can help to identify treatment candidates that may be already in existence.

Just last week there was an announcement about New York University scientists who uncovered a new approach to stimulating the body’s own resident stem cells to repair myelin. They found that by blocking a molecule present in specific stem cells, they were able to stimulate myelin repair and some recovery in mice with an MS-like disease. In the process, they uncovered a new pathway for stimulating myelin repair and are now working to refine the approach to develop a therapy that may be used to repair myelin in people with MS in the future.

It is exciting to see further results from these and other teams, and I’m hopeful that the breadth of research progress we are seeing will yield a therapeutic option that can repair damage and restore function to people with MS.

Be sure to watch for upcoming blogs from ECTRIMS, including some that will focus on innovative wellness and rehab strategies, stem cells, and emerging therapies.

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Claude

Claude Schofield, PhD

Dr. Claude Schofield is Director of Discovery Research at the National MS Society. He began his career as a biomedical researcher, focused on the nervous system. He research has been published in Journal of Neuroscience, Proceedings of the National Academies of Science, and Neural Development.