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.
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 humanSMN expression in vivo. METHODS: Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophypatients 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.
Authors: Chitra Iyer; Xueqian Wang; Samantha R Renusch; Sandra I Duque; Allison M Wehr; Xiaokui-Molly Mo; Vicki L McGovern; W David Arnold; Arthur H M Burghes; Stephen J Kolb Journal: J Neuromuscul Dis Date: 2017
Authors: Kathryn J Swoboda; Charles B Scott; Thomas O Crawford; Louise R Simard; Sandra P Reyna; Kristin J Krosschell; Gyula Acsadi; Bakri Elsheik; Mary K Schroth; Guy D'Anjou; Bernard LaSalle; Thomas W Prior; Susan L Sorenson; Jo Anne Maczulski; Mark B Bromberg; Gary M Chan; John T Kissel Journal: PLoS One Date: 2010-08-19 Impact factor: 3.240