Muscular Dystrophy: Exon Skipping Shows Dramatic Effects In Preventing, Treating Muscle-wasting Disease In Mice

UWA Professor Steve Wilton, head of the Molecular Genetic Therapies Group at UWA's Centre for Neuromuscular and Neurological Disorders, was part of a team which included researchers at The University of Oxford and biotech company AVI BioPharma.

The research, published in the journal Molecular Therapy, has demonstrated that a process known as exon skipping has shown dramatic effects in the prevention and treatment of severely affected, dystrophin and utrophin-deficient mice, preventing severe deterioration of the treated animals and extending their lifespan.

Professor Wilton said researchers had spent years on pre-clinical work in their quest to find a cure for muscular dystrophy.

Treatment involves the intramuscular injection of an antisense molecule to restore the production of the protein dystrophin, the absence of which causes DMD. He said studies and research had shown that the ability to skip certain exons in dystrophin could circumvent these dystrophin gene errors and provide a potential treatment for DMD patients.

DMD is a relentlessly progressive and incurable muscle wasting disorder, and one of the most common serious genetic disorders to affect children around the world. Approximately one in every 3,500 boys worldwide is afflicted with Duchenne muscular dystrophy, with one third of cases presenting with no prior family history of disease. DMD is a devastating and incurable muscle-wasting disease associated with specific errors in the gene that encodes dystrophin, a protein that plays a key structural role in muscle fibre function and stability.

Symptoms usually appear in boys before the age of six years. At this age, affected boys have difficulty in keeping up with their peers, may appear clumsy and fall easily. By age 10, boys have difficulty walking, and are confined to a wheelchair by age 12. Eventually, all muscles are affected and patients experience increased difficulty in breathing.

The muscle wasting is relentlessly progressive and death usually occurs before the age of 25. The outpatient cost of care for a non-ambulatory DMD boy is among the highest of any disease. There is currently no effective treatment for DMD, but for the first time in decades, there are a range of promising therapies under development.