Dr. Coetzee addressing an audience

Recent Developments Offer New Hope, Treatment Options

By all accounts, 2010 was a banner year for multiple sclerosis research. The National MS Society, which provided $36 million to support approximately 325 new and ongoing projects in 2010, noted significant advances in three key research approaches — stopping the disease, restoring function and ending MS forever.

These advances are potentially life changing for over 400,000 Americans and more than 2.1 million worldwide with a form MS. In the United States, virtually each hour someone new is diagnosed with multiple sclerosis. While anyone is susceptible to this chronic disease of the nervous system which is believed to be an autoimmune disorder, more than twice as many women as men have MS, and the disease is more prevalent in Caucasians of northern European ancestry. Although not usually terminal, those who live with the disease often face ever-increasing limitations to function and mobility.

Timothy Coetzee, PhD, who was named chief research officer for the National MS Society in January 2011, said 2010 turned out to be a year of major thematic advances in the treatment of MS. “One such advance is that we had the first oral disease-modifying therapy approved for people with MS,” he said of fingolimod (brand name Gilenya™), which won FDA approval this past September for relapsing-remitting MS. Coetzee noted that clinical trials are underway to test the drug’s effectiveness in the primary-progressive form of the disease, as well.

“More treatment options for people with MS are important, particularly for progressive MS and for the newly-diagnosed. Obviously, being able to take a pill is easier than having to inject yourself, but I think what matters most to people is safety and efficacy,” he continued.

Fingolimod capsules were approved for reducing the frequency of clinical relapses and delaying the accumulation of some physical disability in patients with the relapsing form of MS. A new class of therapy, the drug binds to a docking site — sphingosine-1-phosphate receptor or S1P — on immune cells, including both B and T cells. These immune cells have been implicated in causing nervous system damage in MS. Based on research and clinical trials, the drug seems to encourage the immune cells to remain in the lymph nodes instead of migrating to the brain and spine where they actively do damage. It should be pointed out that the long-term safety of fingolimod is still unknown but extension studies are underway.

Coetzee noted large-scale clinical trials are also underway or just completed for several other oral medications including Cladribine and teriflunomide. In the oral Cladribine CLARITY study of 1,326 patients, those on the drug had a relative reduction in the annualized relapse rate of nearly 58 percent compared to the placebo group. Cladribine, which is currently under FDA review, appears to interfere with lymphocyte activity … this subset of white blood cells underlie the immune attacks that cause the unpredictable symptoms of MS. At press time, a decision about whether or not oral Cladribine could be marketed in the United States was anticipated to have been made by Feb. 28.

Also targeted to those with the relapsing form of MS, a two-year phase III trial of teriflunomide known as TEMSO followed 1,088 people with the disease. In comparing two different doses, the trial showed both doses reduced the rate of relapse by up to 31.5 percent vs. the placebo group. At the higher dose, the risk of disability progression was reduced by 29.8 percent compared to placebo, and MRI scanning showed a reduced risk of new MS lesions and reduced disease activity.

While Coetzee said there are multiple clinical trials now underway looking at the efficacy of various mechanisms to stop the progression of the disease, not all come under the traditional pharmaceutical heading.

“You’ve got a lot of agents in trials, but you’re starting to see new variations on this theme … thinking in new ways about managing the immune system.” One such variation is a milkshake infused with intestinal parasites. A small trial out of the University of Wisconsin being supported through National MS Society funding builds off the “hygiene hypothesis,” which presumes a clean environment suppresses the immune system’s need to be stimulated and mount a response to germs and infection. “What we’re finding is the population of bacteria that live in your gut impact the immune system,” said Coetzee. “That’s really a rich area for us to look at.”

To move research forward that is designed to stop MS in its tracks and to end it forever, the Society recently funded two teams to design a large-scale, long-term study to decipher factors that cause MS progression, with an eye toward figuring out how to block those factors. The Society helped create and fund an international research collaborative effort to identify the genes that make people susceptible to MS so that it might ultimately be prevented. The genetics research should provide new therapeutic targets as well, Coetzee noted.

While these research lines continue, it’s also imperative to restore function that has been lost through disease activity. “This is a two-track strategy,” Coetzee explained. “The theme here is trying to repair the damage; and in the interim of repairing the damage, can we find ways to help people have a better quality of life?” he questioned. 

The answer, based on recent developments, is ‘yes.’ Last year, said Coetzee, the FDA approved the marketing of Ampyra^TM (dalfampridine, formerly known as fampridine SR), the first oral therapy developed to treat an MS symptom. “Ampyra rebalances some of the electrical dysfunction that is found in the nervous system,” he explained, adding the drug targets the nerve cells impacted by the electrical dysfunction, which affect mobility.

Hard on the heels of Ampyra came the approval for Nuedexta^TM (dextromethorphan hydrobromide and quinidine sulfate, formerly called AVP-923 from Avanair Pharmaceuticals). Coetzee said the therapy was approved to treat the uncontrollable and inappropriate laughing or crying, known as pseudobulbar affect, that sometimes accompanies MS and certain other disorders.

Other interesting lines of research include work on stem cell implantation, the identification of a molecule that appears to stimulate the brain’s natural ability to repair myelin in rodents, promising results of a small trial using low doses of Naltrexone (the drug approved for treating addiction) to improve mental health quality and lessen pain in MS patients, and a larger study showing significant improvement in quality of life, depression and fatigue when engaging in mindfulness-based meditation.

Coetzee added that the National MS Society has played an important role in spurring commercial drug development efforts through the organization’s Fast Forward subsidiary. “Within the Society, we fund research both within universities and companies. Fast Forward is bridging the gap between university research and drug development. It funds young biotech companies that are developing innovative therapies for people with MS,” he explained. “As opposed to five years ago, now we have the ability and capacity to begin to think about how you would build a therapy to repair the brain or to protect it from future damage.

“We want to be able to restore … or extend ... the natural mechanisms to repair the brain in MS. When I started in MS (16 years ago), people couldn’t even conceive of the idea of therapies or stem cells to rebuild myelin or agents that protect the brain. I’m excited we’re at a place now that we can even have this conversation,” he concluded.

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