AbstractBackgroundValproic acid (VPA) is expected to become an effective therapeutic agent for spinal muscular atrophy (SMA) because of its histone deacetylase inhibitor effect.AimTo evaluate the effectiveness of VPA for SMA.MethodsSeven consecutive Japanese SMA patients (three males, four females) were recruited. Of those, six were type 2 (cases A–E, G) and one was type 3 (case F). One female patient (case E) was aged 2 years and 10 months, whereas the others ranged in age from 15 to 42 years. VPA was administered for 6 months with L‐carnitine. We carried out SMN transcript analysis of peripheral white blood cells, and evaluated using the Modified Hammersmith Functional Motor Scale for SMA (MHFMS), vital capacity (VC), maximum insufflation capacity (MIC), and cough peak flow (CPF) before and at 1, 3 and 6 months after starting treatment.ResultsCases B–E and G completed the study. The final VPA dosage in cases B–D and G was 400 mg/day, whereas that in case E was 100 mg/day. The quantity of the FL‐SMN transcription product showed a tendency to increase. Case E showed a remarkable improvement in MHFMS, and gained motor function to turn from side to side during the study period. Although no significant changes were observed in MHFMS in the older cases, VC, MIC and CPF were improved in those.ConclusionOur findings suggest that VPA treatment is effective for improving MHFMS and respiratory function in some SMA patients. A placebo‐controlled randomized trial is warranted to confirm the efficacy of VPA for SMA.