Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II

Abstract

Introduction: Efforts in basic research have clarified mechanisms involved in spinal cord injury (SCI), and resulted in positive findings using experimental treatments including cell transplantation and drug administration preclinically. Based on accumulated results, various clinical trials have begun for human SCI.

Areas covered: In this review, the authors focus on five investigational drugs: riluzole, minocycline, Rho protein antagonist, magnesium chloride in polyethylene glycol formulation, and basic fibroblast growth factor. All drugs have established safety and tolerability from Phase I clinical trials, and are now in Phase II. They have been proven to have neuroprotective and/or neuroregenerative effects in animal models of SCI.

Expert opinion: To date, diverse drugs have been translated into clinical trials, but none have reached clinical application. A key gap was the lack of reliable biomarkers for SCI to fast-track Phase I/II trials. Furthermore, problems were often due to lack of adequate outcome assessments for both animal models and SCI patients. In order to advance clinical trials more quickly and with greater success, more clinically relevant animal models should be used in basic research. Clinically, it is indispensable to use appropriate outcome measurements and to construct a wide network among clinical centers to validate the efficacy of drugs.

Keywords:

• basic fibroblast growth factor
• clinical trials in Phase II
• magnesium
• minocycline
• Rho protein antagonist
• riluzole
• spinal cord injury

Acknowledgements

The trial for riluzole is supported by AOSpine North America in partnership with AOSpine International, NACTN, the Rick Hansen Institute and the Ontario Neurotrauma Foundation. The trial for minocycline in Canada is supported by the Rick Hansen Institute, and the one in Israel is by Hadassah Medical Organization. The trial for BA-210 is supported by BioAxone BioSciences, Inc. The trial for magnesium chloride is supported by Acorda Therapeutics, Inc. The trial for FGF2 is supported by Asubio Pharmaceuticals, Inc.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

This box summarizes key points contained in the article.