In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.

OBJECTIVE: Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo.

METHODS: Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy patients treated with valproic acid.

RESULTS: Seven of 10 carriers demonstrated increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were elevated in 7 patients and unchanged or decreased in 13 patients.

INTERPRETATION: We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients.