Abstract
X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder characterized by a progressive demyelination of the central nervous system. The marked loss of myelin and oligodendrocytes observed in the disease prompted us to evaluate the therapeutic potential of insulin-like growth factor-1 and neurotrophin-3, two potent inducers of myelin formation and oligodendrocyte survival. Viral vectors engineered to produce insulin-like growth factor-1 or neurotrophin-3 were administrated into the cerebrospinal fluid of an X-linked adrenoleukodystrophy mouse model. We show that viral-based, long-lasting delivery of insulin-like growth factor-1 and neurotrophin-3 significantly halts the progression of the disease and leads to potent protective effect against the demyelination process. Ann Neurol 2009;66:117-122.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily D
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ATP-Binding Cassette Transporters / genetics
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Adrenoleukodystrophy / complications*
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Adrenoleukodystrophy / genetics
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Analysis of Variance
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Animals
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Behavior, Animal / physiology
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Chemokine CCL22 / deficiency
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Dependovirus / genetics
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Disease Models, Animal
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Gene Transfer Techniques
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Genetic Therapy / methods*
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Green Fluorescent Proteins / genetics
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Humans
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Insulin-Like Growth Factor I / cerebrospinal fluid
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Insulin-Like Growth Factor I / genetics*
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Mice
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Mice, Knockout
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Movement Disorders / etiology*
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Movement Disorders / therapy*
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Neurotrophin 3 / cerebrospinal fluid
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Neurotrophin 3 / genetics*
Substances
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ABCD2 protein, mouse
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ATP Binding Cassette Transporter, Subfamily D
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ATP-Binding Cassette Transporters
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Ccl22 protein, mouse
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Chemokine CCL22
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Neurotrophin 3
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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Insulin-Like Growth Factor I