Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

This is a multi-center trial to assess safety and efficacy of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.

This is a multi-center phase II trial of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Subjects will undergo two baseline assessments over 4 to 6 week period, then will be randomized to treatment or placebo for the next six months. All subjects will then be placed on active treatment for the subsequent six month period. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Subjects will undergo two baseline assessments over a four to six week period, followed by one year active treatment with VPA and carnitine. Outcome measures are performed every 3 to 6 months, and include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.