title: Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kaspar
authors.forename: Jerònia
authors.initials: J
authors.lastname: Lladó
authors.forename: Nushin
authors.initials: N
authors.lastname: Sherkat
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D051100:Glial Cell Line-Derived Neurotrophic Factor; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000473:pathology / Q000821:virology; D018482:Muscle, Skeletal / Q000821:virology; D009414:Nerve Growth Factors / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011897:Random Allocation; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology / Q000821:virology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D025801:Ubiquitin / Q000032:analysis
chemical_list: C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008164:Luminescent Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases