Abstract
Objective:
Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo.
Methods:
Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy patients treated with valproic acid.
Results:
Seven of 10 carriers demonstrated increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were elevated in 7 patients and unchanged or decreased in 13 patients.
Interpretation:
We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclic AMP Response Element-Binding Protein / blood*
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Cyclic AMP Response Element-Binding Protein / drug effects*
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Cyclic AMP Response Element-Binding Protein / genetics
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GABA Agents / therapeutic use*
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Gene Expression / drug effects*
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Heterozygote
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Humans
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Muscular Atrophy, Spinal / drug therapy*
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Muscular Atrophy, Spinal / genetics
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Nerve Tissue Proteins / blood*
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Nerve Tissue Proteins / drug effects*
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Nerve Tissue Proteins / genetics
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Pilot Projects
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RNA, Messenger / blood
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RNA-Binding Proteins / blood*
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RNA-Binding Proteins / drug effects*
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RNA-Binding Proteins / genetics
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SMN Complex Proteins
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein
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Valproic Acid / therapeutic use*
Substances
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Cyclic AMP Response Element-Binding Protein
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GABA Agents
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Nerve Tissue Proteins
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RNA, Messenger
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RNA-Binding Proteins
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SMN Complex Proteins
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SMN1 protein, human
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SMN2 protein, human
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein
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Valproic Acid