Abstract
Objective: This systematic review and meta-analysis aimed to investigate the efficacy and safety of valproic acid (VPA) in spinal muscular atrophy (SMA) patients.
Background: SMA is considered as one of the most common autosomal recessive diseases and leading genetic cause of death during childhood. VPA is one of histone deacetylases (HDAC) inhibitors that shows positive effects on SMA in invitro and retrospective studies.
Design/Methods: Eleven electronic search engines/libraries were systematically searched for relevant publications. Studies were screened for eligibility and data were extracted. The protocol was registered in PROSPERO (CRD42017067203).
Results: Among the included nine clinical trials, five studies were included for the meta-analysis (n=126). The overall effect estimate, comparing pre and post treatment with VPA, showed no significant improvement of the gross motor function [SMD = −0.09, 95% CI [−0.34, 0.17], p = 0.51] with no significant heterogeneity. In terms of the change in full length-SMN (FL-SMN), the pooled effect size showed no significant difference between pre and post treatment with VPA [MD = 0.09, 95% CI [−0.08, 0.25], P = 0.29] with no significant heterogeneity detected. Moreover, the pooled effect size showed no significant difference between pre and post treatment with VPA in terms of change in exon 7 lacking SMA [MD = −1.08, 95% CI [−3.41, 1.26], P = 0.37] with significant heterogeneity detected [P < 0.00001; I2 = 97%]. Qualitative synthesis showed that other motor functions were not improved, while respiratory function tests results were controversial.
Conclusions: Our study suggests that VPA has no significant improvement on motor functions for SMA patients. Pulmonary function testing results are controversial among studies, but the results are not conclusive due to major limitations. Thus, more double blinded randomized controlled trials are required to assert upon these findings.
Disclosure: Dr. Doheim has nothing to disclose. Dr. Elshafay has nothing to disclose. Dr. Kassem has nothing to disclose. Dr. ELdoadoa has nothing to disclose. Dr. Holloway has nothing to disclose. Dr. Elbestawi has nothing to disclose. Dr. Abo-elghar has nothing to disclose. Dr. Hirayama has nothing to disclose. Dr. Huy has nothing to disclose.
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