Carolinas HealthCare System

Duchenne Muscular Dystrophy Preclinical and Clinical Trials

Susan Elizabeth Sparks, MD, PhD

Susan Elizabeth Sparks, MD, PhD
Clinical Genetics

Susan Elizabeth Sparks, MD, PhD, with the department of clinical genetics at Carolinas HealthCare System, continues to excel with her efforts in preclinical and clinical trials in Duchenne muscular dystrophy (DMD). Along with Qi Long Lu, MD, PhD, director of the McColl-Lockwood Laboratory for Muscle Dystrophy Research, and the groundbreaking research of the lab, Dr. Sparks is advancing the translational research program in neuromuscular disorders. She is now involved in a phase two study with a local patient with DMD. The patient is one of only 12 in the country selected for this significant study. 

Study 201 was a randomized, double-blind, placebo-controlled clinical study that began at Nationwide Children's Hospital in Columbus, Ohio. Twelve boys ages 7 to 13 with a confirmed genotype responsive to treatment with an exon-51 skipping drug were randomized to one of three arms: 30 mg/kg (n=4), 50 mg/kg (n=4) and placebo/delayed treatment (n=4). Doses of the drug and placebo were administered weekly by an intravenous infusion. 

At week 25, all patients rolled over to study 202, an 18-month, open-label extension study, and placebo-treated patients initiated the drug treatment at 30 mg/kg (n=2) or 50 mg/kg (n=2). Due to travel time and expenses for weekly infusions, local sites were identified for each of the 12 participants. Since that point, Dr. Sparks has been working with the patient and his family and has seen big improvements in his health due to the drug. 

The primary effectiveness endpoint of study 201 and 202 was the increase in novel dystrophin as assessed by a muscle biopsy at weeks 12, 24 and 48, respectively. The primary clinical endpoint was the six-minute walk test, a well-accepted measure of ambulation and clinical function in DMD. A long-term follow-up of study 202 continues to evaluate safety and clinical outcomes including the six-minute walk test. 

Throughout the 84 weeks, the drug was well tolerated and there were no clinically significant treatment-related adverse events, no serious adverse events, hospitalizations or discontinuations. 

Across all patients who were taking the drug and placebo/delayed-treatment cohorts, there is evidence of continued stabilization on clinical laboratory tests, echocardiograms, pulmonary function tests and measures of muscle strength. 

Dr. Sparks is optimistic about this drug and hopes that one day soon it will be made accessible to more patients with DMD. She is working with Dr. Lu to develop therapeutics that would skip different exons in the dystrophin gene to help others affected with DMD. She has seen the positive results in her patient and would like to see this treatment be available for others with DMD. This is a tremendous breakthrough for patients with DMD and personalized medicine.  

About Duchenne Muscular Dystrophy

DMD is a rare, X-linked degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys worldwide. A devastating and incurable muscle-wasting disease, DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30.

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