Making the Jump to Gene Therapy for Pompe's Disease
Highlights from the American Society of Gene Therapy meeting
Seattle, May 30-June 3, 2001
Although enzyme replacement therapy for Pompe's disease (acid maltase deficiency) has been remarkably successful, there's now a gene therapy approach in the works that could prove even more beneficial.
Pompe's disease is a severe muscle-wasting disorder caused by genetic deficiencies in the acid maltase protein, an enzyme that normally breaks down stored sugar in cells, called glycogen. Extremely low levels of acid maltase allow glycogen to accumulate to toxic levels in cardiac and skeletal (voluntary) muscles, leading to cardiac and respiratory failure during the first year of life.
Three babies have escaped that fatal prognosis and remain heart-healthy, thanks to an ongoing clinical trial of enzyme replacement therapy led by former MDA grantees Yuan-Tsong Chen and Andy Amalfitano of Duke University in Durham, N.C. The therapy involves intravenous injections of a modified acid maltase protein, which Chen developed through preclinical studies supported by MDA.
Unfortunately, the injected acid maltase protein is eventually degraded, so enzyme replacement therapy requires injections twice a week. To provide a longer-lasting treatment at less discomfort and less cost, Amalfitano is devising a way to supply muscles with a replacement acid maltase gene.
So far, Amalfitano has packaged the gene into a partially "gutted" adenovirus, one that's had some of its own genes removed so that it's less likely to provoke an immune reaction. He's also shown that intravenous injection of the gutted adenovirus can restore acid maltase to cardiac and skeletal muscles in two animal models of Pompe's disease. After a single treatment with the gene therapy method, both models (mutant mice and quail) showed near-normal glycogen levels in the heart for up to two months - much longer than the effects of enzyme replacement therapy in the animals.
Amalfitano presented those findings on the closing day of the American Society of Gene Therapy meeting in Seattle. He's continuing to test the gene therapy procedure on animal models in preparation for a clinical trial.
Read more highlights from the American Society of Gene Therapy meeting:
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