BENEFICIAL-EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON WOBBLER MOUSE MOTONEURON DISEASE

Recombinant human insulin-like growth factor-I (IGF-I) is being consid ered as a possible therapeutic agent for the treatment of motoneuron d iseases like amyotrophic lateral sclerosis. The neurological mutant mo use wobbler, carries an autosomal recessive gene (wr) and has been cha racterized as a model of lower motoneuron disorders with associated mu scle atrophy, denervation and reinnervation. The purpose of the presen t study was to determine the possible beneficial effect of IGF-I admin istration in this mouse model. Upon diagnosis at 4 weeks of age, affec ted mice and their control normal littermates received human recombina nt IGF-I (1 mg/kg) or vehicle solution, once a day, for 6 weeks. Body weight and grip strength were evaluated periodically during the treatm ent period. Mean muscle fiber diameter on biceps brachii sections, cho line acetyltransferase activity in muscle extracts, and motoneuron num bers in spinal cord sections were determined, IGF-I treated wobbler mi ce showed a marked weight increase from 3 to 6 weeks of treatment in c omparison with placebo treated mutant mice. At the end of the treatmen t, grip strength, estimated by dynamometer resistance, was 40% higher in IGF-I treated versus placebo treated animals. Mean muscle fiber dia meter which is smaller in wobbler mice than in normal mice was increas ed in IGF-I treated mutants. However, in this study the muscle choline acetyltransferase activity and the number of spinal cord motoneurons were unchanged. Thus, IGF-I administration mainly results in a signifi cant effect on the behavioral and skeletal muscle histochemical parame ters of the wobbler mouse mutant.