Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration. Although viral delivery of IGF-I has shown therapeutic efficacy in the SOD1(G93A) mouse model of ALS, clinical trials of IGF-I in ALS patients have led to conflicting results. Here we examine the effects of an IGF-I splice variant, mechano-growth factor (MGF) which has previously been shown to have greater neuroprotective effects than IGF-I in a number of models of neurodegeneration. A mammalian expression plasmid containing either MGF or, for comparison, the IGF-I cDNA sequence was delivered to the hindlimb muscles of SOD1(G93A) mice at 70 days of age, at symptom onset. Treatment with either IGF-I or MGF resulted in a significant improvement in hindlimb muscle strength, and an increase in motor unit and motoneuron survival. Significantly more motoneurons survived in MGF treated mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / physiopathology*
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Amyotrophic Lateral Sclerosis / therapy*
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Animals
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Cell Count
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Disease Models, Animal
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Humans
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Insulin-Like Growth Factor I / biosynthesis
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / therapeutic use*
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Isotonic Contraction / drug effects
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Isotonic Contraction / physiology
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Mice
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Mice, Transgenic
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Motor Neurons / drug effects*
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Motor Neurons / physiology
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Muscle Fatigue / drug effects
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Muscle Fatigue / physiology
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Muscle Strength / drug effects
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Muscle Strength / physiology
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology*
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Organ Size / drug effects
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Organ Size / physiology
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Succinate Dehydrogenase / metabolism
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Superoxide Dismutase / genetics*
Substances
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mechano-growth factor, mouse
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Insulin-Like Growth Factor I
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SOD1 G93A protein
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Superoxide Dismutase
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Succinate Dehydrogenase