Dec 07, 2011
This year saw exciting research progress, with unprecedented opportunities on the horizon and more scientists than ever working on important questions. Several emerging therapies continued to advance through the pipeline, including several large-scale clinical trials focusing on progressive MS. Progress was also made toward the crucial goals of finding ways to restore function and improving quality of life, and toward addressing specific MS symptoms through exercise, meditation, rehabilitation and medications. And our understanding of factors that influence whether a person develops MS deepened this year, bringing us closer to finding ways to prevent the disease.
The National MS Society continues to propel research forward with a comprehensive research strategy. This year we provided nearly $40 million to support over 325 new and ongoing projects, including everything from discovery research to the Society’s commercial drug development efforts through Fast Forward®.
New projects launched include clinical trials testing novel approaches to protecting the nervous system from MS damage; studies of adult stem cells and natural molecules that may stimulate repair of the nervous system to restore function; research on better treatments for symptoms; and studies on viruses and intestinal bacteria that may be involved in triggering immune attacks in people with MS, leading to clues to ending MS through prevention. Download (.pdf) summaries of new research projects launched in spring and fall.
Here is just a small sample of many important, potentially high-impact research results that occurred this year, presented according to three research goals: stopping MS, restoring what’s been lost, and ending MS forever.
STOPPING MS IN ITS TRACKS
Speeding diagnosis -- An international panel revised and simplified the “McDonald Criteria” commonly used to diagnose MS, incorporating new data that should speed the diagnosis without compromising accuracy. The International Panel on Diagnosis of MS, organized and supported by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis, was chaired by Chris H. Polman, MD, PhD (Free University of Amsterdam).
New therapies showing positive results -- Several late-stage, phase III clinical trials in relapsing MS are make their way toward seeking marketing approval. These include oral teriflunomide, oral BG-12, and intravenous alemtuzumab. An application was accepted by the FDA to review teriflunomide for marketing approval. This year there was disappointing news from companies suggesting that they will not pursue oral cladribine and laquinimod because of perceived difficulties in obtaining FDA approval.
Early results support research of parasitic worms to treat MS -- At least two published studies reported results related to parasitic worms, called helminths, and their possible implications for treating MS. Further study, including the second phase of the clinical trial supported by the National MS Society, should determine whether a “probiotic” treatment approach using relatively harmless parasitic worms to alter immune activity will benefit people with MS.
Progress understanding MS damage -- A team of investigators at the Cleveland Clinic, Mayo Clinic, and international collaborators, whose work on the MS Lesion Project was funded in part by National MS Society targeted initiatives including the Promise:2010 campaign, reported that damage to the cortex (the outer part of the brain) was evident in brain tissue samples from 43% of people who went on to develop MS. Understanding the sequence and timing of damaging events in MS should offer new opportunities for stopping disease progression.
Basic research provides new therapeutic targets – Two studies identified a mechanism related to a messenger chemical called GM-CSF that may be necessary for prompting immune attacks in MS-like disease in mice, and, if developed in further research, may serve as a therapeutic target in future clinical trials. The two teams were led by investigators from the University of Zurich and Thomas Jefferson University.
Details on 130 clinical trials in MS released – In its annual listing of Clinical Trials in MS 2011 (.pdf), the National MS Society includes 130 new or recently ended trials of potential therapies. These include several funded by the National MS Society, including a new National MS Society grant to investigators at Johns Hopkins University and other sites will support a controlled clinical trial to see whether vitamin D added to ongoing disease-modifying therapy can further reduce MS activity.
New clinical trials involving people with progressive forms of MS – Several clinical trials were launched involving people with progressive forms of MS. These include:
• A trial by Novartis testing the oral immune modulator fingolimod in primary-progressive MS
• A trial by Biogen-Idec testing the immune modulator natalizumab in secondary-progressive MS
• An NIH trial testing the immune modulator rituximab in secondary-progressive MS
• An NIH trial testing the antioxidant Idebenone in primary-progressive MS
International Progressive MS Consortium launched – This group of MS societies and the MS International Federation met for the first time to establish mutual goals and priorities to drive research and to harness more resources aimed at progressive forms of MS.
RESTORING WHAT’S BEEN LOST
Initiative to repair and protect nervous system propelled progress -- The Nervous System Repair and Protection Initiative, funded through the National MS Society’s Promise: 2010 Campaign, set the stage for translating basic lab discoveries into clinical efforts to restore nerve function in people with MS. The initiative jump-started the field, trained scores of promising young investigators, produced over 180 research papers, and leveraged millions of dollars in new funding. Read results from their final investigator meeting; view a Webcast featuring the researchers and download the final evaluation of progress (.pdf)
FDA approved Botox for treating urinary incontinence in MS and other neurologic conditions -- A new use for Botox® (onabotulinumtoxin A, Allergan, Inc.) was approved, providing an additional treatment option for people with MS or other neurologic disorders who experience urinary incontinence. In clinical trials involving people with MS or spinal cord injury, targeted injections of Botox into the bladder muscle were found to be beneficial and safe.
Research in many types of stem cells continued to progress –
• Cleveland investigators launched a clinical trial testing the safety of transplanting a patient’s own mesenchymal stem cells (derived from bone marrow) to treat relapsing MS.
• The National MS Society’s drug development subsidiary Fast Forward also announced an alliance to fund the development of Athersys’ MultiStem adult stem cell platform for the treatment of MS, including progressive forms, committing up to $640,000 to advance the program to the clinical development stage. Fast Forward has made 15 such investments to fill critical gaps between research discoveries and the drug development process since its inception in 2007.
Future targets identified for growing or repairing nerve-insulating myelin – The molecules “Axin2” and "RXR-gamma" are essential for myelin repair, found researchers from University of California, San Francisco, the University of Cambridge, the University of Edinburgh and elsewhere, who were co-funded by the National MS Society’s Promise:2010 initiative. And scientists at Biogen-Idec and at Case Western Reserve University reported that blocking an inhibitor of myelin-making cells, called death receptor 6, enhanced their survival and ability to repair myelin in mice with MS-like disease.
Most women with MS have normal pregnancies, deliveries and birth outcomes – Investigators at the University of British Columbia, Vancouver, found that adverse pregnancy or birth outcomes did not differ among women with MS when compared with women without the disease in a large study.
Bone health a concern in early MS -- Oslo University Hospital researchers reported that low bone mass was more prevalent among people newly diagnosed with MS, or those with clinically isolated syndrome (a first episode of MS-like symptoms), than among controls without MS. The risk of bone loss had been known for people with MS, but this study showed that it can occur very early, even before MS has been diagnosed.
First year’s progress from MS Societies’ initial studies on CCSVI and MS – Seven multi-disciplinary teams investigating CCSVI (chronic cerebrospinal venous insufficiency) in MS indicated that they were on track to provide essential data and critical analysis as these two-year projects move toward their completion. These studies were launched with over $ 2.4 million from the MS Society of Canada and the National MS Society (USA).
Many factors contribute to quality of life in MS -- American University of Beirut researchers found that quality of life for people with MS is influenced less by physical factors and more by social factors. People with the highest quality of life (QOL) were those who were religious, had higher levels of education, and lived in urban areas. Separately, researchers from St. Michael’s Hospital, Toronto found that higher levels of fatigue, pain, bladder dysfunction and mental health problems were main factors associated with poor QOL in MS. Targeting symptoms early on may help maximize QOL. Read these and other reports from the 2011 American Academy of Neurology meeting.
Walking a problem for many -- A survey conducted by Harris Interactive on behalf of Acorda Therapeutics and the National MS Society suggested that difficulty walking substantially interferes with activities of daily living and quality of life in a majority of people with MS, even in those who have had MS five or fewer years. Of those who had MS-related walking difficulty, 70% called it the most challenging aspect of MS, yet 40% of those surveyed “rarely or never” discussed walking problems with their doctors, supporting the need for early recognition and management of mobility problems experienced by people with MS. Read this and other reports from the ECTRIMS/ACTRIMS conference.
ENDING MS FOREVER
Global consortium doubles number of MS risk genes identified -- The International MS Genetics Consortium and collaborators identified 29 new genetic variants associated with MS, and confirmed 23 others previously associated with the disease, verifying a major role for the immune system in the development of MS. The study was funded by the Wellcome Trust, the National Institutes of Health, the National MS Society and many other organizations. The results are now to be confirmed and expanded in an independent, second large-scale set of cases with a research grant from the National MS Society.
More on the role of vitamin D and sun exposure and MS risk -- Higher levels of sun exposure and higher blood levels of vitamin D were both associated with decreased risk of having a first neurological event that can be the first indicator of MS, according to a large study in Australia whose findings are in line with other evidence. This study was supported by the National MS Society, the National Health and Medical Research Council of Australia, and others.
International summit convened on vitamin D and MS prevention – This Chicago meeting brings together experts to begin constructing a plan for how to design a clinical trial to test whether vitamin D supplements can prevent MS in people at high risk for developing the disease. More details and plans from this December 2011 meeting will be forthcoming. View a webcast to be held in conjunction with this meeting, featuring internationally prominent MS investigators discussing key MS research to follow in 2012.
Vitamin D levels low in African Americans with MS -- African Americans with MS have significantly lower levels of vitamin D than African Americans who do not have MS, says a new study, but these levels are not linked to disease severity, according to investigators at the University of California, San Francisco. The study was funded by a National MS Society/American Academy of Neurologist Clinician Scientist Award, and a research grant funding genetic studies in ethnically distinct populations.
Gene-environment interactions – University of California, Irvine researchers reveal a novel interaction between two genes that influence susceptibility to developing MS, certain environmental factors, and a chemical process (called N-glycosylation) that modifies the structure of molecules, which together may contribute to our understanding of how complex interactions lead to the development of MS. The team was funded in part by the National MS Society.
Women more likely to carry specific MS-related gene, says large study – University of Oxford and Canadian researchers traced MS in 1,055 families, reporting that a gene long known to have association to MS susceptibility (HLA-DRB1*15) may be more likely to be found in women with the disease than men, and that women with this gene variation may be more likely to transmit it to other women in their families than to men. If confirmed by other investigators, the findings might help explain why women are more likely than men to develop MS, and reinforce the idea that factors other than genes, such as the environment, influence whether a person develops MS.
New studies collecting data aimed at ending MS forever:
• The possibility that children diagnosed with MS may offer a window to early triggering events is the basis of a new study led by Dr. Emmanuele Waubant (University of California, San Francisco), who heads one of six centers in the network of Pediatric MS Centers established by the National MS Society. The multi-site study, now recruiting participants, will investigate possible environmental triggering factors including common viral infections, vitamin D levels, exposure to smoking and others;
• Investigators at the University of California, San Francisco, are recruiting African Americans with MS and their family members across the country for studies aimed at identifying genes that make people susceptible to MS;
• Researchers from the Harvard Medical School, Brigham and Women’s Hospital, and Partners Multiple Sclerosis Center are recruiting 5,000 people who have at least one first-degree relative with a diagnosis of MS. The goal is to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.
These and many other advances this year helped move us closer to a world free of MS.