Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis

Systematic review and evidence-synthesis framework for progressive multiple sclerosis, especially secondary progressive MS. The evidence base included clinical trials in MS, with some relapsing-remitting MS studies, plus trials in Alzheimer disease, motor neuron disease/ALS, Parkinson disease, and Huntington disease, along with preclinical experimental autoimmune encephalomyelitis data.

This systematic review did not test one supplement regimen; it evaluated licensed oral neuroprotective candidates for secondary progressive multiple sclerosis, including ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and a polyunsaturated fatty-acid class (including linoleic acid, lipoic acid, omega-3 fatty acids, and Max EPA oil). The review used clinical and preclinical evidence to nominate oral agents for further clinical evaluation.

The review identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated-fatty-acid class as lead oral candidates for further testing in secondary progressive MS. Fluoxetine had the clearest direct MS signal in the provided text: one mainly relapsing-remitting trial showed a significant reduction in relapse rate incidence and new inflammatory lesions, and another progressive-cohort trial showed favorable trends including reduced EDSS scores and improved 9 Hole Peg Test performance. The authors present this as an evidence-led repurposing pipeline rather than definitive proof of efficacy.

The evidence base was heterogeneous across diseases, populations, and mechanisms, so much of the support is indirect rather than SPMS-specific. The provided text reports no per-arm sample sizes, dosing details, or pooled effect estimates, and the authors note potential publication bias and the need for further evaluation before phase 3 trials.