Gene Therapy

Gene transfer using genes that will produce angiogenic (new blood vessel) growth hormones can potentially help stimulate the body’s natural ability to grow new blood vessels in ischemic heart conditions (when the heart is not getting enough oxygen-carrying blood). Researchers are evaluating angiogenic gene therapy in people with coronary artery disease (CAD), whose own natural angiogenic response may be not be enough to fully restore blood flow around narrowed or blocked arteries due to atherosclerosis.

The potential of angiogenic gene therapy
Successful gene therapy is contingent on the development of safe and effective methods of transferring genes into cells. Genes are inserted into a person’s cell via a carrier known as a “vector.” The most common types of vectors used in gene therapy are viruses, which have the natural ability to deliver therapeutic genes and gene segments into host cells and to use the host’s own cell machinery to produce proteins necessary for cell function and survival.

For example, a viral vector is being used in the Berlex study of an experimental angiogenic gene therapy product, Ad5FGF-4. In the study, patients with angina (chest pain) due to CAD will randomly (chosen by the flip of a coin) receive either Ad5FGF-4 or a placebo via a one-time intracoronary injection by heart catheterization. If Ad5FGF-4 is injected, angiogenic genes are transported by a modified version of a common cold virus (adenovirus) through arteries and capillaries directly to the heart muscle. If gene transfer occurs, angiogenic growth factor protein may be produced, stimulating angiogenesis. Newly created blood vessels then may provide alternate paths for oxygen-rich blood to flow around narrowed or blocked arteries due to atherosclerosis.

Risks associated with angiogenic gene therapy may be related to the route of administration (e.g., bleeding or inflammation), the vector (e.g., inflammation), or the growth-factor protein (e.g., unwanted growth in existing tumors in other areas of the body).

Cardiovascular gene therapy data to date have shown no clinically significant evidence of inflammatory or other complications, including death—regardless of the use of a viral or non-viral vector. Administration of Ad5FGF-4 appears to be safe and well tolerated.