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

Cunniffe, N; Vuong, KA; Ainslie, D; Baker, D; Beveridge, J; Bickley, S; Camilleri, P; ... Coles, A; + view all (2020) Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry 10.1136/jnnp-2020-324286. (In press). Green open access

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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.

Type: Article
Title: Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2020-324286
Publisher version: http://dx.doi.org/10.1136/jnnp-2020-324286
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10116139
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