Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis

M. Vesterinen, Hanna ; Connick, Peter ; M. J. Irvine, Cadi ; S. Sena, Emily ; J. Egan, Kieren ; G. Carmichael, Gary ; Tariq, Afiyah ; Pavitt, Sue ; Chataway, Jeremy ; R. Macleod, Malcolm ; Chandran, Siddharthan (2015)
  • Publisher: Figshare
  • Related identifiers: doi: 10.1371/journal.pone.0117705
  • Subject: Uncategorised | neurodegenerative disorders | max epa oil | evidence | neurodegenerative diseases | sclerosis.designsystematic review | candidate interventions | evaluate candidate oral neuroprotective interventions | secondary progressive multiple sclerosis objectiveto | neuroprotective drugs | systematic approach | neuroprotective therapies | repurposing trials | candidate identification | drug rescue | drug repurposing | lipoic acid | ms | summary data

<div><p>Objective</p><p>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.</p><p>Design</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.</p></div>
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