|Title||Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Vesterinen HM, Connick P, Irvine CMJ, Sena ES, Egan KJ, Carmichael GG, Tariq A, Pavitt S, Chataway J, Macleod MR, Chandran S|
|Keywords||Administration, Oral, Clinical Trials as Topic, Disease Progression, Drug Repositioning, Humans, Multiple Sclerosis, Neuroprotective Agents|
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.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC4391783|
|Grant List||NC/L000970/1 / / National Centre for the Replacement, Refinement and Reduction of Animals in Research / United Kingdom|