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.