The ALS Treatment of Riluzole is Enhanced by Nitric Oxide Inhibition

The Ice Bucket Challenge has raised much awareness and donations for Amyotrophic Lateral Sclerosis (ALS). Every day an average of 15 people are diagnosed with ALS. ALS and other neurodegenerative diseases are affected by nitric oxide (NO), a free radical. A normal level of NO may protect neurons, but an excess level of NO is toxic. Riluzole, the only Food and Drug Administration approved treatment for ALS, prolongs patient’s life by 2-4 months. The modest effect of Riluzole raises concern regarding Riluzole effectiveness. This project investigates the effect of combining Riluzole with NO inhibition using a nitric oxide synthase (NOS) inhibitor. If Riluzole is used with a NOS inhibitor, N_w-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in the planarian model system, then the combination treatment will prolong the life of the planarians more than the individual treatment. The NO levels, measured using the Griess nitrate colorimetric assay, increased by 1.1-fold and 1.8-fold when the planarians were respectively treated with either 5 mM glutamate or 5 mM g-aminobutyric acid (GABA). The survival time of GABA-stimulated planarian increased by 42% in 5 mM L-NAME and 33% in 5 uM Riluzole. The combination of both treatments increased the survival time by 71% indicating an additive effect of Riluzole and NO inhibition in prolonging life. Dose-response analysis with increasing concentrations of L-NAME from 0 to 7.5 mM improved survival time linearly by 11 hours/mM L-NAME. This project indicates there is an additive effect of Riluzole and nitric oxide inhibition in prolonging life.