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Ann Neurol. 2003 Nov;54(5):647-54.

Valproic acid increases SMN levels in spinal muscular atrophy patient cells.

Author information

1
Neurogenetics Branch, National Institute of Neurologic Diseases and Stroke/NIH, Building 10, Room 3B-14, MSC 1250, 10 Center Drive, Bethesda, MD 20892, USA. sumnerc@ninds.nih.gov

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.

PMID:
14595654
DOI:
10.1002/ana.10743
[Indexed for MEDLINE]

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