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Research Advocate
The April 2012 annual meeting of the American Academy of Neurology included more than 500 scientific presentations and display posters focused on research to stop MS, restore function, and end MS forever. The MS sessions were often standing-room only, and appear to get bigger every year. For free access to the conference abstracts (brief summaries), go to www.abstracts2view.com/aan/.
Stopping MS:
Among studies reported were these first results from late-phase III clinical trials. If these treatments are found by the FDA to be safe and beneficial, some of them may come on the market in 2012 and 2013.
- BG-12 (Biogen Idec) – The phase III CONFIRM trial of this oral therapy was reported on during the AAN conference, and is featured in a separate article below. (Abstract P04.136) The results are promising.
- Alemtuzumab (Genzyme/Sanofi) – The two-year CARE-MSII phase III trial compared intravenous alemtuzumab against standard dosing of Rebif® in 840 people with relapsing-remitting MS who had relapsed while on prior therapy. The relapse rate was reduced by 49 percent compared to Rebif, and the risk of disability progression was reduced by 42 percent. (Abstract S01.004) Genzyme plans to file for FDA approval in the second quarter of 2012.
- Gilenya® (fingolimod) – Novartis established a registry of 500 pregnant women collecting information on maternal, fetal, and infant outcomes associated with accidental exposure to Gilenya during pregnancy. This is an FDA requirement that helps to determine whether therapies are safe for pregnant women. (Abstract P06.189)
- Predicting response to therapy – An international team analyzed DNA from individuals who participated in a clinical trial of Copaxone (FORTE trial). Using advanced technology, in preliminary results they were able to identify an array of gene signals that could predict high response to Copaxone. This study is an example of a growing trend to seek ways to optimize treatment choices for people with MS by looking at their genetic underpinning. (Abstract IN3-2.003)
Restoring What’s Been Lost:
Understanding how MS damages the nervous system and how symptoms impact daily life can help to take full advantage of the variety of rehabilitation and exercise regimens that may restore and support function for people with MS.
- Cognitive rehabilitation – Letizia Panicari (San Raffaele University, Milan) and team used functional MRI in a controlled 12-week study, and found increases in brain activity for the group engaged in computer-assisted cognitive rehabilitation, and decreased activity in the control group. (Abstract S51.003)
- Ultrasound study: CCSVI – Andrew Barreto, MD, Jerry Wolinsky, MD, and colleagues (University of Texas Health Science Center at Houston) reported on preliminary results from a National MS Society-supported CCSVI study. They reported finding 3.88 percent of people with MS met at least two criteria for CCSVI, in contrast to 7.14 percent of people who did not have MS – a difference that was not statistically significant. The prevalence of CCSVI using this team’s rigorous techniques is less than previously reported by other groups. (Abstract S10.005)
- Pathology study: CCSVI – Preliminary results were presented in a poster from an ongoing study of vein structure in autopsy specimens (by Claudiu Diaconu, Dr. Robert Fox and colleagues, Cleveland Clinic, Ohio). In this unblinded study, funded by the National MS Society, abnormalities inside the vein tubes (lumen) that drain the brain, and a variety of structural abnormalities and anatomic variations were identified in both people with MS and the control groups. These studies do not support the hypothetical theory that venous insufficiency plays an etiological role in causing MS. (Abstract P05.125)
- BIIB033 (anti-LINGO-1, Biogen Idec) – Blocking the nervous system molecule LINGO-1 increases myelin repair in mice. In the first human trial of this approach, the authors conclude that the results support advancing this myelin repair strategy into a phase II clinical trial. (Abstract P02.021)
- Smartphone to track MS progression – Sashank Prasadd, MD (Brigham and Women’s Hospital, Boston) and team presented a new series of studies that will evaluate whether smartphones can actually monitor MS disease progression. The consortium has created 21 custom applications for the Android smartphone platform, including MS-related questionnaires and specific tests of vision and cognition. The intent is to define outcome measures that more accurately track MS and MS progression in clinical trials. (Abstract P01.144)
Ending MS Forever:
Understanding risk factors that influence who gets MS, and also what course their MS will take, is crucial for finding ways to prevent MS and progression of symptoms.
- Gender differences and vitamin D – Men with low blood levels of vitamin D (less than 30ug/mg) may be more susceptible to MS disability, according to a study of 500 people with different types of MS, conducted by John Rose, MD, and colleagues (University of Utah, Salt Lake City). They also found that women with vitamin D deficiency (less than 20ug/mg) had significantly higher MRI-detected active brain lesions if they had a genetic marker that is common in people with MS (HLA-DR2). (Abstract S50.004) Again, Vitamin D is a “low hanging fruit” – likely important to progression, risk, and treatment of MS.
These and many other presentations reflect the rapid pace of MS research focusing on stopping MS, restoring function, and ending MS forever.
The Road of a Researcher
By Marcella Durand
“There wouldn’t have been a career, otherwise,” he says. “I had no research track record — the Society really took a chance on me.”
It was a chance that paid off big time. Dr. Ransohoff’s research into the role of “chemokines,” messenger proteins that play a role in the immune system, may lead to new MS therapies. For his groundbreaking research, he was chosen by his peers as the 2012 John Dystel Prize recipient. The prize is given jointly by the Society and the American Academy of Neurology.
The Role of Chemokines
In 1993, not too long after he received the Weaver Award, Dr. Ransohoff made the discovery that chemokines played an important role in MS.
He and a colleague, Mari Tani, MD, at the Cleveland Clinic had been studying mice with EAE, an MS-like disease, when they found that astrocytes, a type of brain cell, were producing chemokines that attracted immune cells to the mice’s brains. “It was like the disease process sat up and talked to us,” he remembers. His team then went on to study chemokines in immune cells from people with MS, where they found chemokine receptors on many of the cells involved in the immune attack.
Paving the Way
Dr. Ransohoff also showed that chemokines may actually help determine whether nervous system repair occurs during the course of MS. By deactivating a chemokine receptor called “CXCR2,” he found that the development of myelin-making cells was improved.
“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,” said Benjamin M. Segal, MD, one of the nominators of Dr. Ransohoff for the Dystel Prize.
With a research grant from the Society, Dr. Ransohoff is now studying cell types with and without chemokine receptors to clarify how these cells participate in tissue damage and — with an eye toward developing a future therapy to stop disease activity — tissue repair. He also is returning the Society’s long-ago gesture of trust by mentoring young researchers and teaching them how to talk about their discoveries. “The theoretical and conceptual side of science is invisible unless you communicate it,” he says.
Marcella Durand is the associate editor of Momentum, the Society’s national magazine
BG-12 New Drug Application
Biogen Idec announced that it submitted a new drug application to the U.S. Food and Drug Administration for approval to market oral BG-12 (dimethyl fumarate) for the treatment of MS, based on positive results from several clinical trials involving people with relapsing-remitting MS.
BG-12 is thought to inhibit immune cells and molecules and may be protective against damage to the brain and spinal cord. It has shown to significantly reduce the proportion of people with MS who experienced relapses in a study of more than 1,200 people with relapsing-remitting MS, and significantly reduced the average number of annual MS relapses in a trial of more than 1,400 people with relapsing-remitting MS. Data were presented at the 2011 joint meeting of the European and Americas Committee for Treatment and Research in MS, and at the Annual Meeting of the American Academy of Neurology in April 2012; abstracts can be viewed on the meeting web site.
“If the FDA’s review of oral BG-12 finds it to be safe and effective, it would represent an important treatment advance for people with MS,” said Aaron Miller, MD, Chief Medical Officer of the National MS Society.