Journal of Multiple Sclerosis

Ups and Downs in MS Therapeutics

Abdul Aftab and Pankaj Majlumdar*

Over the past three decades, there has been a remarkable surge in the approval of drugs for treating Multiple Sclerosis (MS), with the number now exceeding 15 options, including various dosages and generics. However, while these treatments have primarily targeted the inflammatory activity underlying relapses, the progressive aspects of MS, characterized by a gradual worsening of disability without relapses, remain inadequately addressed. Siponimod and Ocrelizumab have emerged as crucial drugs approved for treating progressive forms of MS, particularly primary progressive and secondary progressive MS. Despite their benefits for patients experiencing clinical relapses or displaying disease activity in MRI scans, their use is limited to those with active disease as per regulators in the US and Europe. This leaves a significant treatment gap for patients with progressive MS lacking active disease. Addressing this gap, Jeremy Chataway and colleagues conducted a multi-arm phase 2b trial named the Multiple Sclerosis Secondary Progressive Multi-Arm Randomization Trial (MS-SMART), as reported in The Lancet Neurology. The trial selected three experimental drugs—amiloride, fluoxetine, and riluzole—based on an extensive systematic review of 532 potential treatment options. These drugs target axonal pathology and neuroprotection and boast a robust safety profile in humans, rendering them suitable candidates for testing in progressive MS. This study underscores the urgent need for more effective treatments to fill the existing gap in care for patients with progressive MS, particularly those without active disease