• Nick Cunniffe, Khue Anh Vuong, Debbie Ainslie, David Baker, Judy Beveridge, Sorrel Bickley, Patrick Camilleri, Matthew Craner, Denise Fitzgerald, Alerie G de la Fuente, Gavin Giovannoni, Emma Gray, Lorraine Hazlehurst, Raj Kapoor, Ranjit Kaur, David Kozlowski, Brooke Lumicisi, Don Mahad, Björn Neumann, Alan Palmer, Luca Peruzzotti-Jametti, Stefano Pluchino, Jennifer Robertson, Alan Rothaul, Lyndsey Shellard, Kenneth J Smith, Alastair Wilkins, Anna Williams, and Alasdair Coles.
• Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK ngc26@cam.ac.uk.
• J. Neurol. Neurosurg. Psychiatr. 2021 Mar 1; 92 (3): 295-302.

ObjectiveTo 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).MethodsWe 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.ResultsFrom 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.ConclusionsWe report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

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