Cited by 872Amyotrophic Lateral Sclerosis ResearchNeurogenetic and Muscular Disorders ResearchVirus-based gene therapy research

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

Kaspar, Brian K., Lladó, Jerònia, Sherkat, Nushin, Rothstein, Jeffrey D., Gage, Fred H.·2003·Science

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.

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Crossref · 10.1126/science.1086137

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31 of 31 references verified0 citation errors · 0 not checkable

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Authors
Kaspar, B. K., Lladó, J., Sherkat, N., Rothstein, J. D., & Gage, F. H.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Corresponding author
Gage, Fred H.
Venue
Science
Published
2003-08-08
Volume
301
Issue
5634
Pages
839-842
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2002104055
Cited by
872
References
31
Citations by year
2026: 4 · 2025: 11 · 2024: 17 · 2023: 10 · 2022: 14 · 2021: 17 · 2020: 14 · 2019: 27 · 2018: 19 · 2017: 19 · 2016: 36 · 2015: 55 · 2014: 39 · 2013: 45 · 2012: 47
FWCI
44.75
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG 12992, R01AG021876, AG21876, P01AG012992)
  • National Institute of Neurological Disorders and Stroke (NS 33958, R01NS033958)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
amyotrophic lateral sclerosis, insulin-like growth factor I, adeno-associated virus, motor neurons, neurotrophic factors, survival extension, disease progression
MeSH terms
Superoxide Dismutase-1, Dependovirus, Amyotrophic Lateral Sclerosis, Animals, Base Sequence, Cell Count, Disease Models, Animal, Genetic Vectors, Insulin-Like Growth Factor I, Luminescent Proteins, Male, Mice, Transgenic, Molecular Sequence Data, Motor Neurons, Nerve Growth Factors, Proto-Oncogene Proteins, Random Allocation, Spinal Cord, Superoxide Dismutase, Genetic Therapy, Apoptosis, Protein Serine-Threonine Kinases, Gene Transfer Techniques, Disease Progression, Muscle, Skeletal, Caspases, Ubiquitin, Green Fluorescent Proteins, Proto-Oncogene Proteins c-akt, Glial Cell Line-Derived Neurotrophic Factor, Mice, Caspase 9

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