Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuronopathy (pmn)

The neuroprotective drug riluzole (Rilutek(R)) is a sodium channel blocker and anti-excitotoxic drug which is marketed for the treatment of amyotrophi c lateral sclerosis (ALS). Previous studies have shown that riluzole prolon gs survival of transgenic mice harboring the mutated form of Cu,Zn-superoxi de dismutase found in familial forms of the human disease. In this study we have examined the effect of treatment with riluzole in mice suffering from progressive motor neuronopathy (pmn), a hereditary autosomal recessive was ting disease which shares some symptoms of ALS. These mutants display hind limb weakness starting during the 3rd week of Life and leading to paralysis and death during the 7th week of life. Daily treatment with 8 mg/kg of ril uzole by oral route significantly retarded the appearance of paralysis, inc reased life span and improved motor performance on grip test and electromyo graphic results in the early stage of the disease. There was no effect of r iluzole on weight gain. These data demonstrate that riluzole significantly prolongs life span, retards the onset of paralysis and slows the evolution of functional parameters connected with muscle strength in the pmn mouse mo del of motor neuron disease. (C) 2000 Elsevier Science B.V. All rights rese rved.