Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy

In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy

This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro.

This is an open label phase I/II trial of valproic acid in 40 SMA subjects > 2 years of age with severe, intermediate, and mild phenotypes. Primary outcome measures includes laboratory and physical examination assessments to monitor effects on liver, hematologic, metabolic and nutritional status. Secondary outcomes includes measures of gross motor function; electrophysiologic measures of denervation; DEXA estimates of body composition, bone mineral density and content; measures of pulmonary function; and quantitative SMN mRNA and protein levels in blood cells. Subjects will need 2-3 baseline visits over a 3 -6 month period prior to enrollment. Follow-up visits will be scheduled at 3, 6 and 12 months on treatment.

Inclusion Criteria:

• Patients must have a diagnosis of SMA, confirmed by genetic testing
• Only patients 2 years of age and older at enrollment will be eligible

Exclusion Criteria:

• Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications
• Patients taking medications which may interact with VPA
• Patients on ventilatory support for more than 16 hours per day
• Patients currently enrolled in other treatment trials