TY - JOUR
T1 - Drug repurposing
T2 - a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis
AU - Vesterinen, Hanna M.
AU - Connick, Peter
AU - Irvine, Cadi M. J.
AU - Sena, Emily S.
AU - Egan, Kieren J.
AU - Carmichael, Gary G.
AU - Tariq, Afiyah
AU - Pavitt, Sue
AU - Chataway, Jeremy
AU - Macleod, Malcolm R.
AU - Chandran, Siddharthan
PY - 2015/4/9
Y1 - 2015/4/9
N2 - 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.
AB - 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.
KW - oral neuroprotective drugs
KW - evidence based framework
KW - secondary progressive multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84928812195&partnerID=8YFLogxK
UR - https://journals.plos.org/plosone/
U2 - 10.1371/journal.pone.0117705
DO - 10.1371/journal.pone.0117705
M3 - Article
C2 - 25856304
AN - SCOPUS:84928812195
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0117705
ER -