"Vigilant Vector" Design to Sense and Prevent Heart Attacks

Originally Published MDDI May 2002

R&D DIGEST

The number of Americans suffering from some form of heart disease is approaching 62 million, according to the American Heart Association. And at least 12.6 million of those individuals suffer from coronary heart disease. Now a gene therapy technique developed by a group at the University of Florida (UF; Gainesville, FL) could provide an important tool for both diagnosing and treating heart attack patients.

The researchers describe the new technology as a tiny biological machine that could one day be injected into heart attack–prone patients, where the devices would recognize and stop new heart attacks. In its early trials, the University of Florida team used a viral material to deliver a combination of genes to animal heart tissue, where the vector was shown to protect the tissue from heart attacks.

According to the researchers, the virus was capable of sensing when the heart tissue began to undergo hypoxia. It then switched on the protective genes, which prevented ischemia.

The Florida researchers suggest that their method of using such "vigilant vectors" to transmit gene switches eventually could be used to treat a number of other disorders such as diabetes and stroke.

Says Ian Phillips, principal investigator, and professor and chairman emeritus of the university's College of Medicine's department of physiology, "The concept is that we give an IV injection, and although the vector goes everywhere in the body, it only works in the heart or other targeted organ or tissue." He adds, "It just waits there until the right moment arrives to help the person."

Phillips explains that the group adapted the concept of "antisense" genes, used to prevent high blood pressure, to treating heart attacks. The UF researchers used the adeno-associated virus, a commonly used gene carrier, to insert the cardio-protective gene switch. They describe the approach as a classic example of using bionanotechnology for therapeutic purposes, according to Phillips.

Two years were required to develop the gene switch using a combination of genes from human and yeast cells, Phillips explains. The switch, which is active only in heart tissue, activates the protective genes during the four- to six-hour window when hypoxia can cause ischemia. The heart cells are thus protected while oxygen levels are reduced. When the hypoxia ends, the switch turns off again.

The researchers say the technique has been found to be successful in animal tissue cultures and on a limited basis in experiments with live rats; however, Phillips speculates that human studies remain several years away. The researchers used components derived from yeast cells to increase production of the gene switch 300-fold, which is important because large amounts of the genes are needed to reduce the effects of ischemia, Phillips said.

Although no gene therapy treatment using the adeno-associated virus (AAV) virus has been approved for use in humans, clinical trials are under way for a number of diseases, including cystic fibrosis. After one treatment is approved, Phillips believes that others should follow more easily, because the method would remain similar.

Says Phillips, "If you have a new use for a drug already in the market, it's much easier than getting a new drug into the market. The same will be true with the AAV virus."

Copyright ©2002 Medical Device & Diagnostic Industry