Rasagiline for the Treatment of ALS: a randomized controlled study

Objective: To determine whether rasagiline can slow disease progression and to validate a potential new mitochondrial biomarker in patients with ALS. Background: Rasagiline, a monoamine-oxidase B inhibitor approved for the treatment of Parkinson’s Disease, may be neuroprotective in ALS by its action on stabilizing mitochondria. Rasagiline slowed disease progression in the SOD1 mouse model, and in a case series slowed the rate of progression on the ALS functional rating scale-revised (ALSFRS-R). In our prior open label screening trial of rasagiline in ALS we found rasagiline to be well tolerated and to demonstrate possible mitochondrial biomarker engagement. Design/Methods: We conducted a 12 month randomized placebo-controlled clinical trial of 2 mg oral rasagiline compared to placebo at 10 medical centers in the United States between September 2012, and October 2016. Participants were randomized to rasagiline or placebo in a 3:1 ratio. Our primary outcome measure was the twelve month slope of decline of the ALSFRS-R. Secondary outcome measures included adverse event monitoring, mitochondrial biomarkers, respiratory vital capacity, a fall diary, and the ALS global quality of life question. Results: One hundred and three patients were screened, and 80 were randomized. Participants were mostly male (78.8%) and the age range at baseline was 29–76 years of age. Last patient completed in October and the results will be presented at the meeting. Conclusions: Rasagiline may be neuroprotective in patients with ALS. We conducted a randomized placebo controlled clinical trial to determine if rasagiline slows disease progression in ALS and to validate potential new mitochondrial biomarkers. Study Supported by: This study was funded by an FDA Orphan Products Division R01 FD003739. Additional funding was provided in part by Grants UL1 TR 000001 from the University of Kansas Medical Center Clinical and Translational Science Awards (CTSA). JS work is supported by KL2TR000119. Disclosure: Dr Barohn received personal compensation for activities with Grifols u0026 Genzyme as a member of the Speakers Bureau and NuFactor as a consultant. Dr. Statland has received personal compensation for activities with Sarepta, ATYR Bristol Meyers Squib, Acceleron, Clinical Mind, and Novartis as a advisor and/or consultant. Dr. Moore has nothing to disclose. Dr. Walsh has nothing to disclose. Dr. Mozaffar has received personal compensation for activities with Sanofi Genzyme, Grifols, Amicus, Biomarin, Idera Pharmaceuticals and Ultragenyx. Dr. Mozaffar has received research support from Cytokinetics, Alexion, Amicus, Biomarin, Grifols, GlaxoSmithKline, Ultragenyx, and Novartis. Dr. Elman has nothing to disclose. Dr. Nations has received personal compensation for activities with Hilton Pharmaceuticals. Dr. Mitsumoto has received personal compensation for activities with Cytokinetics, Shinogi Pharma, and Biogen. Dr. Fernandes has nothing to disclose. Dr. Saperstein has received personal compensation for activities with Grifols, Baxter, NuFactor, and Corintian as a speaker, consultant, and partial owner. Dr. Hayat has nothing to disclose. Dr. Herbelin has nothing to disclose. Dr. Karam has received personal compensation for activities with Patient Care America as speaker honorarium. Dr. Karam has received personal compensation in an editorial capacity for WriteClick Neurology. Dr. Martens has nothing to disclose. Dr. Dilek has nothing to disclose. Dr. Atchity has nothing to disclose. Dr. Katz has nothing to disclose. Dr. Herbelin has nothing to disclose.