Valproic acid increases SMN levels in spinal muscular atrophy patient cells

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 SMN1at a critical nucleotide such that the majority of SMN2transcripts lack exon 7 and encode an unstable, truncated protein. Here, we show that valproic acid increases levels of exon 7–containing SMNtranscript and SMN protein in type I SMA patient–derived fibroblast cell lines. Valproic acid may increase SMN levels both by activating the SMNpromoter and by preventing exon 7 skipping in SMNtranscripts. Valproic acid and related compounds warrant further investigation as potential treatment for SMA. Ann Neurol 2003;54:647–654