Across the United States and worldwide, there are hundreds if not thousands of scientists and clinicians who are conducting multiple sclerosis research, and advancing our understanding of the MS disease process, its probable causes, more effective treatments, and potential avenues for cure.
To recognize the remarkable work of outstanding MS researchers, each year the National Multiple Sclerosis Society and the American Academy of Neurology jointly award the John Dystel Prize for Multiple Sclerosis Research. The award honors John Jay Dystel, the son of National MS Society Board member Oscar Dystel and his late wife Marion, whose promising career as an attorney was cut short by progressive disability from MS.
This year, Professor Richard M. Ransohoff, MD, of the Cleveland Clinic’s Lerner Research Institute and Mellen Center for MS Treatment and Research, was chosen by a committee of his peers to receive the John Dystel Prize for Multiple Sclerosis Research.
Dr. Ransohoff was honored for pioneering work in MS that led to new insights on immune activity in the brain and spinal cord (neuroimmunology), particularly the role of messenger proteins known as “chemokines.”
Thomas Lane, PhD (University of California, Irvine), who nominated Dr. Ransohoff, said “The insights that Dr. Ransohoff’s discoveries have provided could ultimately pave the way for the development of a new class of drugs in MS based on chemokines.”
Dr. Ransohoff’s most far-reaching research contributions are in applying the study of the role of chemokines – (pronounced KEEmoekynz) messengers that act as attractants – in the immune attack on the brain and spinal cord that occurs in MS. (The FASEB Journal 1993;7(6):592-600) (The Journal of Clinical Investigation 1999;103(6):807-815)
Dr. Ransohoff has also shown that chemokines may actually help determine whether nervous system repair occurs during the course of MS. Along with colleague Robert Miller, PhD, Dr. Ransohoff showed that deactivating a docking site or receptor for chemokines, called “CXCR2,” … allowed for myelin repair. (The Journal of Neuroscience 1998;18(24):10457-10463) Dr. Ransohoff has continued to research CXCR2 and his findings indicate it to be a promising target for therapeutic strategies aimed at stimulating nervous system repair. (The Journal of Neuroscience 2010;30(27):9074-83)
CXCR2 is a drug target with compounds in clinical trials for indications other than MS, so these findings may lead to innovative strategies that address both the immune attack and myelin damage in MS. Dr. Ransohoff’s research indicates that chemokine receptors like CXCR2 are present and functional on both immune cells and resident brain cells. He is now funded by a research grant from the National MS Society to study different cell types with and without chemokine receptors to clarify how some of these cells participate in tissue damage and – importantly – tissue repair. This novel approach should lead directly to effective new therapeutic approaches to stop damaging disease activity in MS.
Sharing knowledge: Dr. Ransohoff is a world leader in translational neuroimmunology, authoring several books and more than 300 publications in peer reviewed journals. He has served on many advisory boards, including the National MS Society’s National Clinical Advisory Board and previously, serving as chair of one of the Society’s Scientific Peer Review Committees. In 2009, Dr. Ransohoff was honored for his service to the Society’s Ohio Buckeye Chapter with induction into the Society’s National Volunteer Hall of Fame. His has served on the chapter’s Board of Trustees and chaired its Clinical Advisory Committee.
Dr. Ransohoff is sought after to speak about neuroimmunology, and has provided hundreds of invited lectures and presentations worldwide since 1997. He organized the first NIH/NINDS “Workshop on Chemokines and MS” and recently was invited to chair the Nervous System section of the Cell Press Inaugural Symposium on “Inflammation and Disease.” Dr. Ransohoff reviews papers for numerous peer reviewed medical journals. He introduced a Clinical Neuroimmunology section into The Journal of Neuroimmunology, served as a Highlights Editorial Advisor for Nature Reviews Immunology (2006-2011), and currently serves on the Editorial Advisory Board for Trends in Immunology, and as Associate Editor of Neurology.
Early in his career, Dr. Ransohoff received a Harry Weaver Neuroscience Scholarship from the National MS Society and a Clinical Investigator Development Award from the National Institutes of Health. He also has been repeatedly listed in the “Best Doctors in America.” Dr. Ransohoff has mentored dozens of young men and women who are engaged in scientific research, or serving as practicing neurologists, around the globe.
New Findings at AAN Meeting
by Marcella Durand
In April, over 12,000 neurologists and researchers gathered in New Orleans to present the latest research in multiple sclerosis at the American Academy of Neurology’s annual meeting. Here are some highlights.
A phase III trial of experimental oral therapy BG-12 found that the average annual relapses over two years in 1,430 people with relapsing-remitting MS was reduced by 44 to 51 percent over placebo. Disability progression was not reduced significantly. The most common adverse events reported were gastrointestinal events and reddening; a small study in 56 people taking BG-12 found that pretreatment with aspirin reduced the latter. However, whether long-term use of aspirin in combination with BG-12 is effective and well-tolerated has yet to be determined. Biogen Idec applied to the FDA in February 2012 for marketing approval of BG-12 to treat MS.
In a phase III trial that compared intravenous alemtuzumab against standard dosing of Rebif (interferon beta-1a), the relapse rate in 840 people with relapsing-remitting MS was reduced by 49 percent or the risk of disability progression reduced by 42 percent. Genzyme plans to file for FDA approval of alemtuzumab for MS in the second quarter of 2012.
Results of a phase III trial of Gilenya (fingolimod) indicated that a daily dose reduced the relapse rate by 48 percent compared with placebo in 778 people with relapsing-remitting MS. Gilenya is the first oral disease modifier for MS to be approved by the FDA.
First results from a clinical trial testing a combination of Copaxone and Avonex showed some evidence that they were better together than either therapy alone. However, the combination was not superior in reducing relapses or progression of the disease.
In a separate study, researchers were able to identify gene signals in people who had participated in a clinical trial of Copaxone that could predict a high response from the therapy. This may point the way for future research on optimizing MS treatment choices.
A study of a green tea extract called Polyphenon E given to 10 people with relapsing-remitting or secondary progressive MS found a 13 percent increase in average levels of a molecule that reflects nerve tissue integrity. The researchers are now conducting a phase II study to determine safety and neuroprotective effects in 48 people.
Restoring What’s Lost
Researchers have found that blocking LINGO-1, a nervous system molecule, increases myelin repair in mice. The first human trial evaluated the safety of the approach in 42 people with relapsing or secondary-progressive MS. Researchers reported no serious adverse events and support moving this repair strategy to a phase II clinical trial.
After a prominent food and wine critic with MS developed a decrease in taste, researchers at the Mount Sinai School of Medicine looked further into this lesser-known symptom of MS, called dysgeusia. In seven case reports of people with MS with dysgeusia, MRI revealed lesions in a small area of the brain stem. In some cases, loss of taste had been the first MS symptom, meaning it may be an important signal.
Ending MS Forever
In a study of 500 people with MS, researchers found that men with low vitamin D may be more susceptible to disability, while women with low levels of the vitamin had more brain lesions if they had a genetic marker common to people with MS. The study points to possible gene and gender influences in vitamin D levels and the risk of developing MS.
For more AAN news, visit www.nationalMSsociety.org/research.
Marcella Durand is on the staff of Momentum, the Society’s national magazine.
New Study on Marijuana
A clinical trial of 37 people with MS with spasticity resistant to standard medications found that the half who smoked marijuana once a day experienced significant improvement compared to placebo. However, the researchers also found that participants showed significantly reduced thinking ability after smoking marijuana. The Society is currently supporting a clinical trial of different forms of cannabis products to test their ability to relieve MS-related spasticity.