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

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.

• 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
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0117705 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25856304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents

Topics

• Administration, Oral
• Clinical Trials as Topic
• Disease Progression
• Drug Repositioning (methods)
• Humans
• Multiple Sclerosis (drug therapy)
• Neuroprotective Agents (administration & dosage, pharmacology, therapeutic use)