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Found: Potential new way to predict some multiple-sclerosis patients’ disease course, drug response

I See Nothing"I have multiple sclerosis. Will I become crippled in the future? Or is it going to be the 'mild' form? Of the dozen medications out there to treat MS, which one is the best therapy for me?"

Stanford neurologist May Han, MD, who specializes in MS, encounters questions like these from her patients on a daily basis. MS is an autoimmune disease of the brain and spinal cord that causes paralysis, blindness and other disabling symptoms. Over a million people, most of them young adults in the prime of life, suffer from MS worldwide.

While there's currently no cure for MS, by the end of 2013 there will be 10 FDA-approved MS therapies. The wealth of choices creates a daunting task for physicians: How can they pick the most appropriate therapy for MS patients?

Despite these therapies’ overall efficacy in preventing MS attacks, any one of them can simply fail to work in a particular patient, or cause debilitating and, sometimes, fatal side effects. Right now, physicians lack tools to predict who would respond well to a specific therapy. That’s largely because, Han told me, different patterns of immune mechanisms go awry in different patients:

Despite great strides in MS research over the past 50 years, these differences in immune response from one patient to the next remain poorly understood. As a result, MS still is a disease where the term “only time will tell” perfectly applies. We do not have methods that allow us to predict responses to a selected therapy.

But Han and her colleagues have achieved an important step toward the goal of finding ways to do just that, as reported in a new study in Nature Immunology. Using cutting edge technology to analyze autopsy samples from MS patients, the study authors (including Stanford geneticist Michael Snyder, PhD) identified more than 2,000 proteins that were activated in MS lesions. One of those proteins, sphingosine-1-phosphate receptor 1, was activated only in the MS brain samples, suggesting its importance in MS pathogenesis.

In fact, Gilenya, the first oral medication ever approved for MS, targets that very receptor. Gilenya wards off MS attacks by preventing immune cells from leaving the spleen and lymph nodes. But some patients on the drug, paradoxically, develop worsening MS attacks.

In a mouse version of MS, the authors discovered that certain mutations in the gene coding for the receptor lead to a worsening of MS symptoms. The new findings raise the possibility that these mutations' presence might contribute to patients' lack of response to therapy when they’re given drugs such as Gilenya.

Developing a diagnostic test to spot the identified gene mutations might help to predict, for those patients who have them, the course of their disease and response to therapy.

Previously: Two different types of MS, one big step toward personalized medicine, Stanford neuroimmunologist discusses recent advances in MS research and Tool could help predict onset of disability for patients with progressive MS
Photo by garryknight

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