Abstract
The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1(G93A) mice. We observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Age of Onset
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Amyotrophic Lateral Sclerosis / genetics*
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Amyotrophic Lateral Sclerosis / pathology
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Amyotrophic Lateral Sclerosis / physiopathology
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Amyotrophic Lateral Sclerosis / prevention & control*
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Animals
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Dependovirus / physiology
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Disease Models, Animal
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Female
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Green Fluorescent Proteins / metabolism
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Injections, Spinal / methods
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Insulin-Like Growth Factor I / administration & dosage*
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Insulin-Like Growth Factor I / metabolism
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Male
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Mice
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Mice, Transgenic
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Motor Neurons / pathology
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Neuroprotective Agents / administration & dosage*
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Neuroprotective Agents / metabolism
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Psychomotor Performance / physiology
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Sex Factors
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Spinal Cord / physiology*
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Superoxide Dismutase / genetics
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Time Factors
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Transduction, Genetic
Substances
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Neuroprotective Agents
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Green Fluorescent Proteins
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Insulin-Like Growth Factor I
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SOD1 G37R protein, mouse
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Superoxide Dismutase