Drug repurposing : a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis

Vesterinen, Hanna M. and Connick, Peter and Irvine, Cadi M. J. and Sena, Emily S. and Egan, Kieren J. and Carmichael, Gary G. and Tariq, Afiyah and Pavitt, Sue and Chataway, Jeremy and Macleod, Malcolm R. and Chandran, Siddharthan (2015) Drug repurposing : a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis. PLoS ONE, 10 (4). e0117705. ISSN 1932-6203 (https://doi.org/10.1371/journal.pone.0117705)

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Abstract

Objective: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. Design: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action. Results: We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation. Conclusions: We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

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