1. Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.
- Author
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Cunniffe N, Vuong KA, Ainslie D, Baker D, Beveridge J, Bickley S, Camilleri P, Craner M, Fitzgerald D, de la Fuente AG, Giovannoni G, Gray E, Hazlehurst L, Kapoor R, Kaur R, Kozlowski D, Lumicisi B, Mahad D, Neumann B, Palmer A, Peruzzotti-Jametti L, Pluchino S, Robertson J, Rothaul A, Shellard L, Smith KJ, Wilkins A, Williams A, and Coles A
- Subjects
- Animals, Drug Evaluation, Humans, Drug Repositioning, Multiple Sclerosis, Chronic Progressive drug therapy
- 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., Competing Interests: Competing interests: DB received compensation for consultancy activity from Canbex Therapeutics, Japan Tobacco, Lundbeck, InMune Bio, Merck, Novartis, and Roche in the past 3 years. AC received honoraria and travel support from Genzyme (a Sanofi company) prior to 2017. MC has received honoraria for educational events and/or consultancy from Biogen, Merck, Roche, AbbVie and Novartis. GG has received compensation for serving as a consultant in relation to multiple sclerosis drug development from AbbVie, Actelion, Atara Bio, Biogen, Celgene, EMD Serono, Japanese Tobacco, Sanofi-Genzyme, Genentech, GlaxoSmithKline, GW Pharma, Merck KGa, Novartis, Roche and Teva. LH holds a small number of GSK shares as part of her renumeration when she was an employee, which she left 4 years ago. DM received consultancy fees from Biogen, MedDay and SanofiGenzyme and Novartis. BN holds a patent regarding the treatment of demyelinating diseases including metformin: WO2019/206419 A1, Treatment for demyelinating disease. SP is cofounder, CSO and shareholder (>5%) of CITC Ltd and iSTEM Therapeutics, and cofounder and non-executive director at Asitia Therapeutics. LP-J is Head of Research at iSTEM Therapeutics. AW receives research support from Roche not associated with drug development or use., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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