SPECIFIC AND EFFICIENT GENE-TRANSFER STRATEGY OFFERS NEW POTENTIALITIES FOR THE TREATMENT OF MOTOR-NEURON DISEASES

SEVERAL growth factors are candidates for the therapy of motor neurone diseases. However, there is no efficient, safe, and practicable admin istration route which hampers the clinical use of these potentially th erapeutic agents. We show that specific and high yield gene transfer i nto motor neurones can be obtained by peripheral intramuscular injecti ons of recombinant adenoviruses. These vectors are retrogradely transp orted from muscular motor units to motor neurone cell bodies. Gene tra nsfer can thus be specifically targeted to particular regions of the s pinal cord by appropriate choice of the injected muscle. The efficienc y of gene transfer is high, with 58-100% of the motor neurones afferen t to the injected muscle expressing the transgene. This new therapeuti c protocol allows specific targeting of motor neurones without lesioni ng the spinal cord, and should avoid undesirable side effects associat ed with systemic administration of therapeutic factors.