GENE-THERAPY OF MURINE MOTOR-NEURON DISEASE USING ADENOVIRAL VECTORS FOR NEUROTROPHIC FACTORS

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy cause progressive paralysis, often leading to premature death. Neurotrophic factors have been suggested as therapeut ic agents for motor neuron diseases, but their clinical use as injecte d recombinant protein was limited by toxicity and/or poor bioavailabil ity. We demonstrate here that adenovirus-mediated gene transfer of neu rotrophin-3 (NT-3) can produce substantial therapeutic effects in the mouse mutant pmn (progressive motor neuronopathy). After intramuscular injection of the NT-3 adenoviral vector, pmn mice showed a 50% increa se in life span, reduced loss of motor axons and improved neuromuscula r function as assessed by electromyography. These results were further improved by coinjecting an adenoviral vector coding for ciliary neuro trophic factor. Therefore, adenovirus-mediated gene transfer of neurot rophic factors offers new prospects for the treatment of motor neuron diseases.