Introduction: Spinal Muscular Atrophy(SMA) is an autosomal recessive neuromuscular disorder due to loss-of-function of SMN1 gene. Valproate(VPA), a histone deacetylase(HDAC) inhibitor,increases SMN expression bytranscriptionalactivation and appropriate splicing of SMN2 gene (potential therapeutic target). Possible improvement in strength and/or motor function has been reported by 3 open-label trials and 1 RCT of VPA in human subjects.

Methods: Double-blinded RCT was conducted at tertiary-care centre in Northern India (2012-2016). Sixty children(aged 2-15years)were randomized 1:1 to Group1(placebo+placebo) and Group2(valproate+carnitine); received treatment for 52weeks. Patients were assessed for muscle power by MMT (primary outcome), motor function using Modified Hammersmith Functional Motor Scale (MHFMS) and pulmonary function(FVC) at baseline,12,24,36 & 52weeks. Patients were monitored for adverse drug effects. Serum valproate level was done at 52 weeks.

Results: Two groups were comparable in baseline characteristics including MMT and MHFMS. Seventeen patients were lost to followup. There was no significant difference in change in muscle power, motor function and pulmonary functions at 12,24,36 and 52weeks between the two groups. Dyspepsia was the most common side effect(27%(8/29) in group1 and 20%(20/25) in group2). Weight gain, dysphoria, fatigue and sedation were also reported but none was significantly different between both the groups. No clinically significant hematological or biochemical adverse effect was reported.

Conclusion: Valproate and levocarnitine combination given for 52 weeks is not efficacious compared to placebo in improving muscle strength and motor function in SMA type 2 and 3 patients.