By Sean Henahan, Access Excellence

NEW ORLEANS (Nov 12, 1996) Successful results introducing a missing gene into animal and human tissue bodes well for gene therapy prospects for a fatal childhood heart disease, report researchers.

Working in the laboratory, the scientists used an adenovirus vector to introduce a gene that produces an enzyme missing in the muscle cells of children with a rare genetic condition known as Pompe's disease. One injected, the gene produced the missing enzyme in muscle cells for an extended period of time. This is the first demonstration of long-term production of the normal enzyme without toxicity. The results offer the possibility of single treatment by this method, the researchers say.

Pompe's disease causes cardiomyopathy (an enlargement and weakening of heart muscle) in infants. Because of a genetic defect, an essential enzyme is missing from the heart muscle cells of infants with the disease.

The Hopkins scientists were able to isolated the defective gene and then insert it in a short-lived and otherwise harmless type of adenovirus which then carried the normal gene's DNA into mice and into human muscle cells in the laboratory. The cells came from children who died of Pompe's disease.

"In principle, we know a single gene disorder could be treated by replacing a defective gene," says Paul D. Kessler, M.D., an assistant professor of medicine at Hopkins. "But the problem has always been a lack of good vectors for getting the normal gene into cells long term."

The Hopkins group used an adeno-associated virus to deliver the gene for the enzyme acid alpha-glucosidase. Healthy DNA was injected into muscles in the mice and began producing the enzyme two weeks later and continued to produce it for at least three months. More animal studies are planned.

"These results demonstrate that adeno-associated viral vectors can effectively transfer genes into muscles in animals and lead to sustained expression of a therapeutic protein," says Barry J. Byrne, M.D., Ph.D., assistant professor of pediatric cardiology at Hopkins.