Susan T. Iannaccone, MD, FAAN
Jimmy Elizabeth Westcott Distinguished Chair in Pediatric Neurology
Professor of Neurology and Pediatrics, University of Texas Southwestern Medical Center
Director of Child Neurology, Children's Medical Center
Director of Neuromuscular Disease and Neurorehabilitation, Texas Scottish Rite Hospital for Children


1. Title: Clinical Trials for Pediatric Spinal Muscular Atrophy
Funding: NIH/Westat CRO

Spinal muscular atrophy (SMA) is a genetic disease of the anterior horn cell with a frequency of 8 per 100,000 live births. There is a high mortality during infancy so that prevalence is greatest during mid and late childhood. Death almost always is secondary to severe restrictive lung disease that is progressive, although muscle weakness may be stable over decades. There is no known treatment for SMA. Until recently, no therapeutic trials have been attempted. New information regarding the nature and function of the SMN protein and the availability of new pharmacological agents now make it possible to consider clinical trials in this disease.

The study is part of the NIH NPTUNE project to conduct translational research in SMA. There is a parallel effort for drug development. Infants and children ages 3 months-12 years will receive phenylbutyrate, a histone deacetlyase inhibitor, for safety and pharmacokinetic studies. Patients will be seen at frequent intervals for monitoring of adverse events.

In another Phase II study, patients aged 2-12 years will be randomized to treatment with valproic acid, hydroxyurea or placebo. Patients will be monitored for safety and effectiveness using clinical and biological outcome measures.

2. Title: Phase II study for efficacy and safety of PTC124 in Duchenne muscular dystrophy
Funding: PTC Therapeutics

This is clinical trial of PTC124, an exon skipping inducing drug, in DMD patients with stop codon mutations in the dystrophin gene. Ambulatory boys aged 5 years and up who are on a stable dose of prednisone will be eligible for this trial. They will receive this oral treatment and be seen regularly for monitoring for safety and efficacy using clinical and biological outcome measures.

3. Title: Genotype/phenotype comparison in a pediatric cohort of Charcot-Marie-Tooth disease (hereditary sensory motor neuropathy)
Funding: TBD

Possibly the largest clinic for children with CMT includes more than 150 patients seen at CMCD and TSRHC. About 50% of the patients carry the duplication of the PMP22 gene (diagnosis CMT1A). The other 50% carry one of about 8 known gene mutations or an unknown mutation. The clinical variability in terms of presentation and course is remarkable and could yield valuable information for families and patients. This could be a combination retrospective and prospective review of the this population.