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Science 301 (5634): 839-842

Copyright © 2003 by the American Association for the Advancement of Science

Retrograde Viral Delivery of IGF-1 Prolongs Survival in a Mouse ALS Model

Brian K. Kaspar,1 Jerònia Lladó,2* Nushin Sherkat,1 Jeffrey D. Rothstein,2 Fred H. Gage1{dagger}

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.

1 Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2 Departments of Neurology and Neuroscience, Johns Hopkins University, 600 North Wolfe Street, Meyer 6-109, Baltimore, MD 21287, USA.

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* Present address: Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Hospital Son Dureta, C/Andrea Doria 55, Edifici D 1a planta, 07014 Palma, Illes Balears, Spain.

{dagger} To whom correspondence should be addressed. E-mail: gage{at}

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