Pilot trial of phenylbutyrate in spinal muscular atrophy.
The aim of this study was to evaluate tolerability and efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy (SMA). Ten patients with SMA type II confirmed by DNA studies (age range 2.6-12.7 years, mean age 6.01) were started on oral PB (triButyrate) in powder or tablets. The dosage was 500 mg/kg per day (maximum dose 19 g/d), divided in five doses (every 4 h, skipping one night-dose) using an intermittent schedule (7 days on and 7 days off). Measures of efficacy were the change in motor function from baseline to 3 and 9 weeks, by means of the Hammersmith functional motor scale. In children older than 5 years, muscle strength, assessed by myometry, and forced vital capacity were also measured. We found a significant increase in the scores of the Hammersmith functional scale between the baseline and both 3-weeks (P < 0.012) and 9-weeks assessments (P < 0.004). Our results indicate that PB might be beneficial to SMA patients without producing any major side effect. Larger prospective randomised, double-blind, placebo controlled trials are needed to confirm these preliminary findings.
Mercuri
Eugenio
E
Department of Child Neurology, Catholic University, Rome, Italy. e.mercuri@imperial.ac.uk
Bertini
Enrico
E
Messina
Sonia
S
Pelliccioni
Marco
M
D'Amico
Adele
A
Colitto
Francesca
F
Mirabella
Massimiliano
M
Tiziano
Francesco D
FD
Vitali
Tiziana
T
Angelozzi
Carla
C
Kinali
Maria
M
Main
Marion
M
Brahe
Christina
C
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004334:Drug Administration Schedule; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018908:Muscle Weakness / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D010654:Phenylbutyrates / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D020127:Recovery of Function / Q000187:drug effects; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology
D010654:Phenylbutyrates