Valproate and spinal muscular atrophy (Review).

Childhood spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in the survival motor neuron (SMN) gene. The severity of the disease is dictated by the copy number of a second copy of the gene, known as SMN2, with higher copy numbers associated with milder forms of SMA. This is because the level of SMN protein produced by patients dictates the severity of the disease. As all patients retain at least one copy of the SMN2 gene, therapeutic strategies are geared towards increasing full-length SMN protein expression from SMN2. One of the identified therapeutic compounds is valproic acid, or valproate (VPA), a histone deacetylase inhibitor (HDACI) that has been used since the 1970s as an anti-convulsant. Here, we discuss VPA's modes of action and potential side effects in the treatment of SMA.