Gene Therapy For The Heart


Angina, or chest pain, occurs when part of the heart muscle doesn't get enough oxygen (a condition known as myocardial ischemia). The most common cause of angina is coronary artery disease – when portions of the heart's arteries are narrowed by deposits of fat and plaque. When a blockage significantly impairs blood flow, the area of heart muscle fed by that vessel is starved for oxygen. Patients may experience an uncomfortable pressure, fullness, or pain in the center of the chest. Sometimes the pain radiates to the jaw, neck, shoulder, back, or arm. Typically, angina occurs when the heart requires extra blood and oxygen, such as during periods of exercise or stress. In severe cases, angina may occur even at rest.

According to the American Heart Association, about six million Americans suffer from angina. It's important for patients to report symptoms to their doctor because chest pain may be a sign of an impending heart attack. There are several different medications that can be used to relieve the symptoms. One of the most common drugs for angina is nitroglycerin. It relaxes the walls of the arteries and allows more blood to flow into the heart muscle. Nitroglycerin also relaxes the veins, keeping a little more blood in the venous circulation and reducing the amount of blood returning to the heart (thus, reducing the workload on the heart). Calcium channel blockers also widen the arteries. Another class of drugs, the beta-blockers, reduces heart rate and the force of contraction, easing the stress on the heart muscle.

When medications are inadequate to control the symptoms of angina, or when coronary artery blockages are severe, doctors may recommend angioplasty. In this procedure, a balloon-tipped catheter is inserted through an artery in the groin and fed through the circulatory system to the area of blockage in the heart. Once in place, the balloon is inflated. As the balloon enlarges, it pushes the plaque against the arterial wall and compresses the build-up, creating a wider passageway through the area. Then the balloon is deflated and withdrawn. Sometimes doctors will insert an expanding hollow metal device, called a stent, into the artery at the time of the balloon inflation. The stent remains open and acts as a secure section of scaffolding, preventing the plaque from swelling and reclosing the artery.

Gene Therapy for the Heart

Sometimes standard therapies don't help patients with angina. In severe cases, doctors may perform a coronary artery bypass. But not all patients are candidates for the surgery. Researchers are now studying another option for angina patients, called angiogenesis. Angiogenesis is the growth of new blood vessels. In the experimental treatment, doctors are trying to get patients to grow new blood vessels in the heart, which would provide more blood to areas affected by ischemic disease.

There are several proteins that control the growth of blood vessels. Some of the proteins lead to the growth of new blood vessels and other inhibit the process. One of the proteins that spurs angiogenesis is fibroblast growth factor (FGF). The gene for FGF is derived from human DNA and replicated in a laboratory. A common cold virus (adenovirus) is used to carry the gene into the cells. To provide the treatment, doctors feed a catheter to the site of a blockage and inject the gene therapy solution. Hopefully, the cells will express the gene and signal the production of the FGF protein that grows new blood vessels.

Currently, gene therapy for angiogenesis is in clinical trials throughout the country. Patients are randomly assigned to receive a high dose, low dose, or a placebo. Doctors want to test both the effectiveness and safety of the treatment. There is a theoretical risk the treatment will lead to uncontrolled growth of blood vessels elsewhere and cause the development of cancer. So patients are thoroughly screened for cancer risk before they are enrolled in the trial. Investigators hope to enroll 500 patients from around the country. For more information or referral to the nearest trial site, call (205) 934-7898.