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.
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Growth factor-mediated prevention of neuronal loss in transection models has predicted protection from disease-specific mechanisms in other models.
“Indeed, growth factor–mediated prevention of neuronal loss in transection models has predicted protection from disease-specific mechanisms in other models22–25.”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [25]
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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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