Scientists Make Progress In Gene Therapy For Heart Disease

November 12, 1996

Johns Hopkins scientists have successfully used a virus to supply a missing gene and its enzyme product to muscle cells in animals and humans for an extended period. The achievement could have implications in the treatment of an inherited fatal heart disease in children called Pompe's disease.

The two Hopkins-led studies are the first to demonstrate long-term production of the normal enzyme without toxicity and therefore the possibility of single treatment by this method. Results will be presented at 9:30 a.m. and 10 a.m., Nov. 11 at the American Heart Association's 69th annual Scientific Sessions in New Orleans.

Pompe's disease, which causes cardiomyopathy (an enlargement and weakening of heart muscle) in infants, is caused by an inherited metabolic disorder. Heart muscle dysfunction results from a missing or defective enzyme (proteins that stimulate chemical reactions in living tissue) caused by a gene mutation.

Hopkins scientists isolated the defective gene in Pompe's disease and, with Avigen, Inc., researchers, used a harmless virus as a vehicle to carry the normal gene's DNA into mice and into human muscle cells in laboratory dishes. The cells came from children who died of Pompe's disease.

Once inserted into the abnormal cells, the healthy gene material replaced the missing enzyme and restored normal enzyme function over a prolonged period.

"In principle, we know a single gene disorder could be treated by replacing a defective gene," says Paul D. Kessler, M.D., senior author and 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. Further 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., lead author and an assistant professor of pediatric cardiology at Hopkins.

Gene therapy involves treating diseases by delivering genes into cells to restore normal cell actions or to stop abnormal cell actions. The genes are delivered by vectors, harmless viruses that enter the target cell, delivering the gene with them.

The studies were supported by the Peter Belfer Laboratories for Myocardial Research at Hopkins, the American Heart Association's Delaware branch, the March of Dimes Birth Defects Foundation and the W.W. Smith Foundation.

--JHMI--

Johns Hopkins Medicine

Related Enzyme Articles from Brightsurf:

Repairing the photosynthetic enzyme Rubisco
Researchers at the Max Planck Institute of Biochemistry decipher the molecular mechanism of Rubisco Activase

Oldest enzyme in cellular respiration isolated
Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration.

UQ researchers solve a 50-year-old enzyme mystery
Advanced herbicides and treatments for infection may result from the unravelling of a 50-year-old mystery by University of Queensland researchers.

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.

Triggered by light, a novel way to switch on an enzyme
In living cells, enzymes drive biochemical metabolic processes. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics.

A 'corset' for the enzyme structure
The structure of enzymes determines how they control vital processes such as digestion or immune response.

Could inhibiting the DPP4 enzyme help treat coronavirus?
Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine.

Bacterial enzyme could become a new target for antibiotics
Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Chemists create new artificial enzyme
Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

First artificial enzyme created with two non-biological groups
Scientists at the University of Groningen turned a non-enzymatic protein into a new, artificial enzyme by adding two abiological catalytic components: an unnatural amino acid and a catalytic copper complex.

Read More: Enzyme News and Enzyme Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.