Valproic acid increases SMN levels in spinal muscular atrophy patient cells
CJ Sumner, TN Huynh, JA Markowitz… - Annals of Neurology …, 2003 - Wiley Online Library
CJ Sumner, TN Huynh, JA Markowitz, JS Perhac, B Hill, DD Coovert, K Schussler, X Chen…
Annals of Neurology: Official Journal of the American Neurological …, 2003•Wiley Online LibrarySpinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutation of
the telomeric copy of the survival motor neuron gene (SMN1). Although a centromeric copy
of the survival motor neuron gene (SMN2) is retained in all patients with SMA, it differs from
SMN1 at a critical nucleotide such that the majority of SMN2 transcripts lack exon 7 and
encode an unstable, truncated protein. Here, we show that valproic acid increases levels of
exon 7–containing SMN transcript and SMN protein in type I SMA patient–derived fibroblast …
the telomeric copy of the survival motor neuron gene (SMN1). Although a centromeric copy
of the survival motor neuron gene (SMN2) is retained in all patients with SMA, it differs from
SMN1 at a critical nucleotide such that the majority of SMN2 transcripts lack exon 7 and
encode an unstable, truncated protein. Here, we show that valproic acid increases levels of
exon 7–containing SMN transcript and SMN protein in type I SMA patient–derived fibroblast …
Abstract
Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutation of the telomeric copy of the survival motor neuron gene (SMN1). Although a centromeric copy of the survival motor neuron gene (SMN2) is retained in all patients with SMA, it differs from SMN1 at a critical nucleotide such that the majority of SMN2 transcripts lack exon 7 and encode an unstable, truncated protein. Here, we show that valproic acid increases levels of exon 7–containing SMN transcript and SMN protein in type I SMA patient–derived fibroblast cell lines. Valproic acid may increase SMN levels both by activating the SMN promoter and by preventing exon 7 skipping in SMN transcripts. Valproic acid and related compounds warrant further investigation as potential treatment for SMA. Ann Neurol 2003;54:647–654
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