Pilot trial of phenylbutyrate in spinal muscular atrophy

Area of Science:

• Neurology
• Genetics
• Pharmacology

Background:

• Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder.
• Current treatments for SMA focus on supportive care and emerging gene therapies.
• Phenylbutyrate (PB) is being investigated for its potential therapeutic effects in neurodegenerative conditions.

Purpose of the Study:

• To assess the tolerability and efficacy of oral phenylbutyrate (PB) in pediatric patients diagnosed with spinal muscular atrophy (SMA) type II.
• To evaluate the impact of PB on motor function, muscle strength, and respiratory capacity in SMA patients.

Main Methods:

• A cohort of ten SMA type II patients (age 2.6-12.7 years) received oral PB (triButyrate) at 500 mg/kg/day.
• Treatment involved an intermittent schedule: 7 days on, 7 days off, with doses every 4 hours during waking hours.
• Efficacy was measured using the Hammersmith functional motor scale at baseline, 3 weeks, and 9 weeks. Muscle strength and forced vital capacity were assessed in older children.

Main Results:

• Significant improvements in Hammersmith functional motor scale scores were observed at both 3 weeks (P < 0.012) and 9 weeks (P < 0.004) compared to baseline.
• Phenylbutyrate (PB) was generally well-tolerated, with no major reported side effects.
• Preliminary data suggest a positive trend in motor function for SMA patients treated with PB.

Conclusions:

• Phenylbutyrate (PB) may offer a beneficial therapeutic option for patients with spinal muscular atrophy (SMA) type II.
• The observed improvements in motor function warrant further investigation.
• Larger, randomized, double-blind, placebo-controlled trials are necessary to confirm the efficacy and safety of PB for SMA.