The phase 2b Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) was thought to be the next best hope for finding a drug therapy to slow neurodegeneration, but it has proved to be another dead end for people with progressive multiple sclerosis (MS). So report the study’s investigators in a new article published online by The Lancet Neurology.
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Amiloride, fluoxetine and riluzole — the three drugs chosen to be tested for neuroprotection — showed the best potential of more than 500 candidate test drugs screened in a systematic review. Nearly 450 patients were randomly assigned treatment with one of these three drugs or placebo over 96 weeks. An impressive 88% of patients completed the study. However, the well-designed, well-executed trial didn’t produce the much-anticipated result: reducing percentage brain volume change as detected by MRI. None of the test drugs performed better than placebo.
Robert Fox, MD, a neurologist with Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, reflected on this outcome in an invited commentary that accompanies the MS-SMART report in The Lancet Neurology.
“These disappointing results raise an obvious question: Why was a promising treatment not identified to carry forward into phase 3 trials?” he writes.
Dr. Fox goes on to offer three possible explanations that correspond with possible modifications for future studies. To ultimately identify an effective therapeutic for progressive MS, he says, researchers first must:
“The negative outcome of MS-SMART, and many other trials in neurodegenerative diseases, points to an urgent need to rethink how we select and test experimental treatments for neurodegenerative conditions,” writes Dr. Fox.
Fortunately, MS-SMART also incidentally shows ways for neurology researchers to redirect their efforts. Hitting a dead end just signals another turn on our continuing journey toward an effective therapeutic for progressive MS.
Image at top shows corticospinal tracts from a diffusion tensor imaging study from a patient with progressive MS.