359 Combinatorial Surgical and Neuroprotective Therapy for Cervical Spondylotic Myelopathy Results in Improved Neurological Function: From Preclinical Proof of Concept to a Phase III Randomized Controlled Trial

Abstract INTRODUCTION Surgical decompression is an effective treatment for cervical spondylotic myelopathy (CSM). However, a number of patients continue to experience substantial neurological impairment post surgery. Riluzole has neuroprotective effects in injuries of the central nervous system. To determine the efficacy of riluzole for promoting neurological improvement in CSM following decompression, we performed a pre-clinical proof of concept experiment and then we translated our work and established a Phase III multi-center randomized controlled clinical trial (CSM-Protect). METHODS Surgical decompression was performed in a rat CSM model and riluzole, or control, was administered. Spinal cord blood flow (SCBF) was evaluated in all CSM rats, in vivo, before and after decompression using FAIR MRI. The long-term outcomes of decompression with or without riluzole treatment determined using neurobehavioural and neuroanatomical assessments. Our multi-center double-blind randomized CSM-Protect trial includes a total of 300 CSM patients undergoing decompression surgery and randomized 1:1 to receive riluzole (2 × 50 mg daily for 14 days before and 28 days post surgery) or placebo treatment. MJOA score will determine the effectiveness of the combinatorial treatment at 6 months following surgery. Statistical analysis will be performed as a sequential adaptive trial with interim analysis. RESULTS >Rats receiving combinatorial treatment displayed long-term significant neurological improvements associated with preservation of motor neurons and corticospinal tracts compared to rats treated with decompression alone. Riluzole also dramatically reduced the extent of ischemia-reperfusion injury post surgical decompression in our animal model. At present, 285 subjects have been enrolled into the CSM-Protect trial. A planned interim analysis using this sample has commenced. CONCLUSION The proposed combinatorial therapy promotes neurological recovery in CSM rats. Confirmation of this proof of concept has been translated from bench to the bedside and we are currently running the CSM-Protect trial to determine the efficacy of this combinatorial treatment option for use in CSM patients.