Conditions: Spinal Muscular Atrophy
Keywords: Spinal Muscular Atrophy SMA Sodium Phenylbutyrate
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 22
Healthy volunteers: no

Brief summary:
In this single-center trial, we will evaluate the effects of NaPB on presymptomatic Spinal Muscular Atrophy (SMA) type I (cohort 1)and presymptomatic SMA type II (cohort 2) infants. A variety of outcome measures will be performed at each study visit to follow the course of the disease. Total duration of the study for type I infants will be 18 months, for type II infants, 24 months.

Detailed description:
Perform a phase I/II study to evaluate effects of sodium phenylbutyrate (NaPB) in a cohort of presymptomatic infants, predicted to develop either SMA type 1 or SMA type 2 given genotype and family history of an older sibling with the respective SMA type. Primary outcomes: 1) to collect additional safety and pharmacokinetic data in neonates and young infants administered NaPB within the dosing guidelines already in use for urea cycle disorder therapy, and 2) to determine possible benefit of early treatment intervention with regard to status of denervation and functional motor status at specific time points for which we have matched natural history data to perform a comparison between cohorts and between each cohort and participants from our natural history database matched for age, SMN2 dosage and gender.

Arms:
arm 1: Treatment with sodium phenylbutyrate; age \< 3 months; history of sibling(s) with type I SMA; SMN2 dosage \< 3 copies arm 2: Treatment with sodium phenylbutyrate; age \< 6 months; history of sibling(s) with type II SMA; SMN2 dosage \< 4 copies

Interventions: intervention 1: Sodium phenylbutyrate
Intervention descriptions: intervention 1: Sodium phenylbutyrate is dispensed as a powder, 450-600 mg/kg/day, divided into four doses. For cohort 1, treatment and monitoring continues for 18 months. For cohort 2, treatment and monitoring continues for 24 months.

Protocol document: