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Stanford Medicine Scope - June 16th, 2016 - by Bruce Goldman
All too often, you read of a basic-research advance that promises to lead to new therapies — and then you never hear about it again. But this time there’s some follow-up to report on the multiple-sclerosis therapy front. That’s good news for the million-plus people, mostly young adults in the prime of life, who suffer from MS worldwide.
In a Nature Immunology study I blogged about in 2013, a team led by Stanford neurologist May Han, MD, showed the importance of S1PR1, a protein preferentially activated in MS patients’ brains which, it turns out, is targeted by Gilenya, the first oral therapy ever approved for MS.
Gilenya, now in wide use as a first-line therapy for relapsing remitting multiple sclerosis, cuts many patients’ relapse rates in half. But other patients getting Gilenya see their condition worsen instead.
In that study of a few years ago, Han’s team identified some variants of the gene coding for S1PR1 that, in mice, were associated with worsening rather than alleviation of MS symptoms in response to Gilenya.
Now, in a new study published in JCI Insight, Han and her colleagues have pinpointed the molecular basis for this defective response to Gilenya among patients with S1PR1 gene variants. Experiments demonstrated that combining the drug with another one (an antibody to another protein called CCR6, found on the immune cells that attack the brain in MS) corrects the molecular defect and restores Gilenya’s efficacy.
The study’s results suggest a two-pronged approach, Han told me. The first is a page torn from the personalized-medicine playbook: Develop a diagnostic that makes it easy to check whether patients carry any mutations in the S1PR1 gene that predispose them to problems with Gilenya. If they’re positive, don’t use that drug as a first-line treatment, at least not alone. The second prong, follows directly from the first: In those doomed by their genomes to be Gilenya non-responders, try combining Gilenya with an anti-CCR6 agent.
Han’s group is planning a clinical study to test that combination. Success would mark another milestone in a multi-year effort to bring biomedical research from the laboratory bench to people in need.
