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

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 PalmerLuca Peruzzotti-Jametti, Stefano Pluchino, Jennifer Robertson, Alan Rothaul, Lyndsey Shellard, Kenneth J Smith, Alastair Wilkins, Anna Williams, Alasdair Coles

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume92
Issue number3
DOIs
Publication statusPublished - 01 Mar 2021

Bibliographical note

Funding Information:
Funding JB received expense payments from Novartis for speaking as patient representative during Siponimod licensing. AC receives funding from the Medical Research Council (MRC) and MS Society UK. DF is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and has a project with Sangamo. AGdlF has been supported by the European Committee for Treatment and Research in MS (ECTRIMS) postdoctoral fellowship during this period. GG declares current research funding from Merck KGa (CLAD-B study), Roche (ORATORIO-HAND study) and Takeda (SIZOMUS Study). DM received funding previously from Biogen, MedDay and SanofiGenzyme. BN received funding from the Cambridge Centre for Myelin Repair, funded by MS Society UK. SP declares current funding from Italian and US Multiple Sclerosis Societies. LP-J has been supported by a senior research fellowship FISM—Fondazione Italiana Sclerosi Multipla—cod. 2017/B/5 and financed or co financed with the ’5five per mille’ public funding, by the Isaac Newton Trust RG 97440 and the Addenbrooke’s Charitable Trust RG 97519. KJS declares current funding from Fondation Leducq, Multiple Sclerosis Society, Rosetrees Trust. AW received a research grant from Sanofy (2018). AW declares funding from MS Society UK, Roche, MRC and Lifearc.

Publisher Copyright:
©

Keywords

  • Animals
  • Drug Evaluation
  • Drug Repositioning
  • Humans
  • Multiple Sclerosis, Chronic Progressive/drug therapy

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis'. Together they form a unique fingerprint.

Cite this