Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside.
Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole is a benzothiazole anticonvulsant with neuroprotective effects. It has been approved by the U.S. Food and Drug Administration as a safe and well-tolerated treatment for patients with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves the inhibition of pathologic glutamatergic transmission in synapses of neurons via sodium channel blockade. There is convincing evidence that riluzole diminishes neurological tissue destruction and promotes functional recovery in animal SCI models. Based on these results, a phase I/IIa clinical trial with riluzole was conducted for patients with SCI between 2010 and 2011. This trial demonstrated significant improvement in neurological outcomes and showed it to be a safe drug with no serious adverse effects. Currently, an international, multi-center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in phase II/III is in progress with riluzole for patients with SCI (clinicaltrials.gov, registration number NCT01597518). This article reviews the pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing preclinical evidence, and emerging clinical data in the treatment of SCI.
Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada. nagoshi@2002.jukuin.keio.ac.jp.|Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan. nagoshi@2002.jukuin.keio.ac.jp.
Narihito
N
Nagoshi
Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada. hirospine@gmail.com.|Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan. hirospine@gmail.com.
Hiroaki
H
Nakashima
Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada. michael.fehlings@uhn.on.ca.|Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada. michael.fehlings@uhn.on.ca.
Michael G
MG
Fehlings
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D009435:Synaptic Transmission / Q000187:drug effects*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D019782:Riluzole