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Valproic acid increases SMN levels in spinal muscular atrophy patient cells
Author(s) -
Sumner Charlotte J.,
Huynh Thanh N.,
Markowitz Jennifer A.,
Perhac J. Stephen,
Hill Brenna,
Coovert Daniel D.,
Schussler Kristie,
Chen Xiaocun,
Jarecki Jill,
Burghes Arthur H. M.,
Taylor J. Paul,
Fischbeck Kenneth H.
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10743
Subject(s) - smn1 , spinal muscular atrophy , sma* , motor neuron , exon , valproic acid , biology , microbiology and biotechnology , cancer research , gene , genetics , spinal cord , neuroscience , epilepsy , mathematics , combinatorics
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