title: Research advances in gene therapy approaches for the treatment of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons that causes progressive muscle weakness, paralysis, and premature death. No effective therapy is available. Research in the motor neuron field continues to grow, and recent breakthroughs have demonstrated the possibility of completely achieving rescue in animal models of spinal muscular atrophy, a genetic motor neuron disease. With adeno-associated virus (AAV) vectors, gene transfer can be achieved with systemic non-invasive injection and minimal toxicity. In the context of this success, we review gene therapy approaches for ALS, considering what has been done and the possible future directions for effective application of the latest generation of vectors for clinical translation. We focus on recent developments in the areas of RNA/antisense-mediated silencing of specific ALS causative genes like superoxide dismutase-1 and other molecular pathogenetic targets, as well as the administration of neuroprotective factors with viral vectors. We argue that gene therapy offers new opportunities to open the path for clinical progress in treating ALS.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, IRCCS' Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, Italy. monica.nizzardo@unimi.it
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.forename: Marianna
authors.initials: M
authors.lastname: Falcone
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Magri
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000628:therapy*; D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000639:trends*; D005822:Genetic Vectors / Q000627:therapeutic use; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use; D034622:RNA Interference; D051381:Rats; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D018696:Neuroprotective Agents; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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