Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis |
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| Authors: | Hanna M Vesterinen Peter Connick Cadi M J Irvine Emily S Sena Kieren J Egan Gary G Carmichael Afiyah Tariq Sue Pavitt Jeremy Chataway Malcolm R Macleod Siddharthan Chandran |
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| Institution: | 1. Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom.; 2. The Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom.; 3. Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom.; 4. National Hospital for Neurology and Neurosurgery, London, United Kingdom.; University of Utah, UNITED STATES, |
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| Abstract: | ObjectiveTo 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.DesignSystematic 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.ResultsWe 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.ConclusionsWe 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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