Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.

DOI: http://doi.org/10.1136/jnnp-2020-324286 Journal: J Neurol Neurosurg Psychiatry E-pub date: 1 Mar 2021 Authors: N Cunniffe, KA Vuong, D Ainslie, D Baker, J Beveridge, S Bickley, P Camilleri, M Craner, D Fitzgerald, AG de la Fuente, G Giovannoni, E Gray, L Hazlehurst, R Kapoor, R Kaur, D Kozlowski, B Lumicisi, D Mahad, B Neumann, A Palmer, L Peruzzotti-Jametti, S Pluchino, J Robertson, A Rothaul, L Shellard, KJ Smith, A Wilkins, A Williams, A Coles

Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.

Abstract:

OBJECTIVE: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS). METHODS: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review. RESULTS: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine. CONCLUSIONS: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.