A team at the University of California at San Francisco led by Jonah Chan, PhD, has identified a group of compounds approved by the U.S. Food and Drug Administration (FDA) for various disorders that might also stimulate myelin repair. They report the findings in Nature Medicine (Published online July 6, 2014). This study was mainly funded by friends of the MS Research Group at UCSF, with additional support from the National MS Society Harry Weaver Neuroscience Scholar Award to Dr. Chan and the UCSF Clinical & Translational Science Institute Catalyst Award for Innovation.
Background: In MS, the immune system attacks and destroys myelin, the fatty substance that surrounds and protects the nerve fibers, and the nerve fibers can also be damaged. Current therapies are largely aimed at dampening the immune system. However, a therapy that repairs damage to myelin and nerve fibers is also necessary.
Decades of research into nerve physiology, MS tissue damage and the biology of glial cells – the numerous brain cells that support nerve cells – have laid the groundwork for finding ways to repair damage and restore normal function in individuals with MS. Achieving this goal is a priority of research supported by the National MS Society.
One challenge in developing repair strategies has been identifying possible therapeutic targets. The fact that compounds need to be observed for their ability to form myelin around nerve fibers has limited the speed at which the impact of compounds could be screened. This study reports on a novel technology developed by Dr. Jonah Chan that could revolutionize the development of myelin repair strategies. In September 2013, Dr. Chan was the first recipient of the Barancik Prize for Innovation in MS Research, a new international prize launched to recognize innovation and progress in MS research, for his pioneering work in applying this technology to the search for ways to stimulate brain repair in people who have MS. Read more
The Study: Dr. Chan’s team invented new nanofiber and micropillar technology to rapidly identify compounds that stimulate the regrowth of myelin. The “Binary Indicant for Myelination on Micropillar Arrays” (BIMA) uses arrays of tiny fabricated “micropillars” that simulate nerve fibers. Myelin-making cells called oligodendrocytes form myelin around each micropillar, looking somewhat like the rings of a tree, enabling an automated readout to permit the team to study functional myelination.
The team initiated a screen using this technology, testing 1000 molecules for their ability to promote oligodendrocyte development and wrapping of myelin around the micropillars. The screen identified a group of eight compounds that are approved by the U.S. Food and Drug Administration to treat various disorders, and are collectively known as anti-muscarinic compounds. Dr. Chan and colleagues followed up by inducing myelin damage in mice and then administering one of these compounds – clemastine, an oral antihistamine used to treat allergy symptoms. Analysis performed 14 days later revealed enhanced development of oligodendrocytes and accelerated myelin repair when compared with untreated control mice.
Based on these findings, a clinical trial of clemastine is now getting underway by the University of California, San Francisco team. Read more
Conclusion: Dr. Chan’s team reports on novel technology that allows for screening thousands of molecules for their potential to repair myelin, and may eventually help to fill this void in the growing arsenal of MS therapies A clinical trial stemming from this approach is now getting underway.
“We are at a pivotal time in MS research,” says Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer for the Society. “This study shows how reversing damage to regain function is almost within our grasp. By confirming and following through on these findings with clinical studies in people, we can change the world for everyone with MS.”
Read more about repairing damaged tissue and watch a webcast featuring Dr. Chan, on “Promising MS Research to Repair, Protect and Restore the Nervous System.”
Read more about this study on the MS Discovery Forum website.
