PREVENTION OF MOTONEURON DEATH BY ADENOVIRUS-MEDIATED NEUROTROPHIC FACTORS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disea se characterized by progressive loss of motoneurons, and has no effect ive treatment, Experimental studies in rodents have shown that motoneu rons respond to a variety of molecules including brain-derived neurotr ophic factor (BDNF), and the glial-cell line-derived neurotrophic fact or (GDNF), Here we investigated the neuroprotective effect of these gr owth factors, encoded by an adenovirus, on the death of axotomized fac ial motoneurons in newborn rats, We used a new gene therapy strategy t hat involves gene transfer to motoneurons by intramuscular injection o f an adenoviral vector, which is retrogradely transported from an inje cted target muscle (Finels et al.,: NeuroReport 7:373-378, 1995). A si gnificant increased survival of motoneurons was observed in animals pr etreated with adenovirus encoding BDNF (34.5%, P < 0.05) ou GDNF (41.9 %, P < 0.05) 1 week after axotomy. These results indicate that pretrea tment with BDNF or GDNF, using this therapeutic strategy, is able to p revent the massive death of motoneurons that normally follows axotomy in the neonatal period, opening new perspectives to limit neuronal dea th in degenerative disorders. (C) 1997 Wiley-Liss, Inc.