Treatment of spinal muscular atrophy by sodium butyrate

Spinal muscular atrophy (SMA) is an autosomal recessive disease characteriz ed by degeneration of the anterior horn cells of the spinal cord, leading t o muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increas es the amount of exon 7-containing SMN protein in SMA lymphoid cell lines b y changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expr ession of SMN protein in motor neurons of the spinal cord and resulted in s ignificant improvement of SMA clinical symptoms. Oral administration of sod ium butyrate to intercrosses of heterozygous pregnant knockout-transgenic S MA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treat ment of human SMA patients.