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Research

 
Research Next Steps

The turn of the year saw MS researchers assessing their progress in a number of areas. A think tank on progressive MS brought together MS investigators, research funding agencies and industry representatives. And, in January, Dr. Timothy Coetzee, chief research officer of the Society (see News), moderated a panel of MS researchers in a live webcast, “Repairing the Nervous System in MS: Progress and Next Steps.”

How does MS progress?

At the think tank, which was hosted by the Society and its commercial drug development entity Fast Forward last December in Boston, Society President and CEO Joyce Nelson pointed out that progressive MS is the centerpiece of the Society’s Strategic Response for the next five years, with a focus on:

  • Researching what leads to disease progression,
  • Finding ways to repair damage to the nervous system,
  • Accelerating the development of new therapies.

Better identification faster

Finding ways to more quickly identify progressive MS based on biology rather than on symptoms would mean therapies could be tested earlier in the course of the disease and possibly protect the nervous system from injury.

Brain GearsSome evidence indicates that nerve degeneration occurs independently of inflammatory events, but there is other evidence that degeneration stops when inflammation subsides. Therefore, more research is needed to understand the cause of underlying nerve damage in progressive MS and to identify new targets for therapies. Participants also discussed the need for biomarkers—“footprints” that could help identify or predict MS progression. Think tank participants reported that steady progress is being made in finding noninvasive ways of detecting nervous system damage and whether protection or repair are taking place.

Additional issues

The participants discussed other important issues, as well. Many clinical trials do not run long enough to make clear whether there is an effect against slow progression. The traditional measurement of disability progression, the EDSS scale, is not sensitive to subtle change, which poses a problem in monitoring progressive MS.

And, some previous trials used a mixed population of people with primary progressive MS and secondary progressive MS. Since it’s not clear that all types of progressive MS would respond the same way, mixing participants may be one reason that some past trials were not successful.

For a complete wrap-up of the meeting and a webcast featuring a panel of several participants, visit www.nationalMSsociety.org/thinktank.

Repairing the nervous system

On January 11, Dr. Coetzee, chief research officer of the National MS Society, was joined by Drs. Peter Calabresi, Ian D. Duncan, Charles ffrench-Constant and Gavin Giovannoni for the webcast, “Repairing the Nervous System in MS: Progress and Next Steps.” The four researchers recently served as leaders of four international teams in the National MS Society’s Nervous System Repair and Protection Initiative, funded through the Promise 2010 campaign.

The investigators discussed research on the ways that nerve fibers, or axons, and their protective myelin coatings are damaged. Certain drugs the experts have studied seem to prevent nerve cells from dying in an animal model. Since some of these drugs are commercially available right now for other diseases, they are good candidates for future clinical trials.

New drugs emerging

The researchers also talked about repairing the nervous system by stimulating the body’s own repair cells to be more active or by trying several types of stem cells to repair myelin. Part of the conversation included how newer approved treatments may help in the battle to protect the nervous system in people with MS.

“For the first time we’re really starting to see the emergence of very, very effective drugs for treating inflammation,”

Dr. Giovannoni said, noting that these therapies might also help to stave off nervous system damage and allow natural repair processes to work, although this has not yet been proven. “We’ve seen people who have highly active disease going on these drugs and improving,” he said.

For a full report or to read a transcript of the webcast, visit www.nationalMSsociety.org/webcasts.


The World of MS Research

In October, more than 5,500 neurologists and other investigators from around the world covered almost every aspect of current MS research in some 900 scientific presentations and posters at the annual ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) conference in Gothenberg, Sweden.

Some research highlights

A newly completed two-year, phase III trial of teriflunomide, an oral compound that inhibits specific immune cells, in 1,088 people with relapsing MS, found positive results. Dr. Paul O’Connor of the University of Toronto reported that two different doses of teriflunomide significantly reduced the rate of MS relapses by up to 31.5% compared to placebo, and that the higher dose reduced the risk of disability progression by 29.8%. It also reduced the risk of new MS lesions and reduced disease activity. Additional clinical trials are under way.

Other medications also show promise at various trial stages. An oral compound called firategrast caused a significant decrease in the rate of new MRI-detected lesions in a six-month trial in relapsing-remitting MS. Ocrelizumab, which targets and kills immune B cells, reduced new lesions by at least 89% over placebo in a 24-week trial.

In a separate session, Dr. Antonio Uccelli of the University of Genoa described attempts to stop MS progression using infusions of an individual’s own bone marrow or blood stem cells (mesenchymal cells). Dr. Uccelli is now collaborating on a study that he hopes will show that these cells are beneficial.

Restoring function

Several research teams reported progress in improving quality of life and specific symptoms, including fatigue and mobility issues, through group physical therapy, and supervised aerobics, yoga and resistance training classes. Another study suggested that memory training can improve brain function. Many reports focused on CCSVI (chronic cerebrospinal venous insufficiency), with mixed or conflicting results. Lab studies identified additional molecules that may block the ability of myelin-making cells to repair damage caused by MS; selectively turning them off could be useful for encouraging myelin repair in people with MS.

Risk factors

Dr. Trond Riise of the University of Bergen reviewed the growing list of factors that may contribute to an individual’s susceptibility to developing MS, and pointed to current studies that may lead to a better understanding of the interactions and variations of these multiple risk factors.

For a more complete report on the conference, search “ECTRIMS” at nationalmssociety.org.


Research Updates

Nerve Repair Teams Convened To Share Exciting Progress and Plan Next Steps

A cure for MS means not just stopping and ending the disease but repairing damage and restoring lost function. The Nervous System Repair and Protection Initiative, funded through the National MS Society’s Promise: 2010 Campaign, was launched in 2005 to address what was then an underexplored area. This bold initiative involved the largest grants ever offered by the Society and set the stage for translating basic lab discoveries into clinical efforts to restore nerve function in people with MS. The results have been impressive: it jump-started the field, trained scores of promising young investigators, produced over 150 research papers, and leveraged millions of dollars in new funding.

New Guidelines for the Use of Plasma Exchange Therapy in MS

New guidelines from the American Academy of Neurology (AAN) recommend that clinicians consider using plasma exchange (also known as plasmapheresis, a blood-cleansing procedure) for a number of conditions for which it has shown benefit. In MS, the guidelines suggest it may be effective as a secondary therapy for exacerbations unresponsive to corticosteroids in people with relapsing forms of MS, and may be useful for severe, rapidly progressive MS and similar disorders (acute fulminant demyelinating CNS disease). The treatment was not found to be effective for secondary-progressive MS or primary-progressive MS.

Risk of Having a First Neurologic Event Is Decreased With Increased Sun Exposure And Higher Blood Levels of Vitamin D, Society-Supported Australian Study Suggests

Higher levels of sun exposure and higher blood levels of vitamin D were both associated with decreased risk of having a first demyelinating event that can be the first indicator of multiple sclerosis. The findings provide additional support for previous suggestions that sun exposure and vitamin D may help protect against developing MS. It remains to be seen whether safe and effective strategies can be developed that utilize this potential protection without the risks involved in overexposure to the sun or overdoses of vitamin D supplements, and whether these findings have relevance for individuals who already have MS.

Warm Weather Impact on Thinking in MS and Other News In Advance Of Neurology Meeting

A study linking warmer weather with problems with thinking tasks in people with MS is among thousands of studies that will be presented at the April meeting of the American Academy of Neurology. This study, conducted at the Kessler Foundation (West Orange, New Jersey) is based on work by postdoctoral fellows trained through the National MS Society’s Mentor Based Fellowship in Rehabilitation Research award to Dr. John DeLuca. The National MS Society will provide a full summary of this and other important presentations after the meeting is concluded.

Update on Tysabri and PML

According to information released by Biogen Idec, as of January 7, 2011 there have been 85 confirmed cases of progressive multifocal leukoencephalopathy (PML, a viral infection of the brain that usually leads to death or severe disability) among people who have used Tysabri® (natalizumab, Biogen Idec and Elan Pharmaceuticals) after it became available for prescription in July 2006. Of the cases, 44 occurred in Europe, 36 occurred in the United States, and 5 occurred in the rest of the world. As of the end of September 2010, 75,500 people worldwide have used Tysabri since it was marketed. According to data released by Biogen Idec, based on the 85 cases, the overall risk of PML is estimated to be 1.06 per 1,000 patients.

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