Gene therapy causes new blood vessels to grow

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Gene therapy causes new blood vessels to grow
Gene therapy causes new blood vessels to grow
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Gene therapy grows new blood vessels

A new therapy, therapeutic angiogenesis, aims to create new blood vessels that represent a natural diversion around blocked blood vessels. It has already been tested on 8 patients with circulatory disorders in their legs. In this therapy, genes, i.e. sections of DNA, are injected into the patient’s leg muscles. These genes are responsible for the production of a growth factor that stimulates the formation of blood vessel cells during the development of the human embryo. The injected DNA stimulates existing blood vessel cells to form new veins. The same growth factor is also released by human tumor cells. The genes for the factor were obtained from a human gland tumor and amplified in Isner's laboratory.

To grow, tumors need a blood supply, said Jeffrey Isner, professor of medicine and pathology at Tufts University School of Medicine and chief of cardiovascular research at St. Elizabeth's Medical Center. Therefore, tumor cells secrete vascular endothelial growth factor, which creates new blood vessels. This factor is also formed by developing embryos. For the injections, the genes were not attached to a virus or other Trojan horse to deliver the DNA into the cells, but rather the naked DNA was administered twice, 4 weeks apart.

Isner announced that the therapy will soon be tested in people whose coronary arteries are narrowed by atherosclerosis. "If this genetic therapy works in the leg, it should work in the heart," says Isner, who in an August 1996 article in the Lancet described his first patient in whom gene therapy produced new blood vessels.

If the new gene therapy proves safe and effective, cardiologists will be able to help patients who may or may not be at risk from balloon angioplasty, bypass surgery, drugs, or other treatments to restore blood flow are successful. Whether this gene therapy will establish itself as a primary treatment - in conjunction with angioplasty, for example, or in place of bypass surgery - cannot be said yet and depends on further research, says Isner. At the moment, gene therapy is helping to avoid amputations in patients with severe atherosclerosis in the legs. Every therapy was tried in the patients who took part in this study, but in vain explains Isner. For patients with severe limb circulatory disorders, amputation is the only way to deal with fatal gangrene of the affected limb.

In this study, no random subdivision into one group treated with gene therapy and the other conventionally was performed because there is no conventional therapy available for people with such severe disease. Critical extremity anemia affects 100,000-200,000 people in the United States, making it the "most commonly underdiagnosed entity in cardiovascular disease," Isner says. It is often blamed on old age, but it can also be a sign that something is wrong with the vascular system. In many of his patients, atherosclerosis is not limited to the peripheral vessels of the limbs, but also affects the function of the blood vessels that supply the heart and brain.

The effectiveness of gene therapy has already been tested using magnetic resonance angiography, which depicts blood flow in the vessels, measurements of blood pressure in the ankle and arm and – where possible – stress tests.

Circulation improved in 8 out of 10 treated legs and new visible vessels were found in 7 out of 10 treated legs.

During the follow-up examinations, which were carried out one to six months after the last injection, the blood pressure at the ankle increased from 0.33 to 0.47 of the ankle index. "The blood pressure when lying down should be the same in the ankle and arm," explains Isner. At the start of the study, the patients' ankle blood pressure was about a third of that measured in the arm. The 14% increase meets the criteria by which the success of surgery and angioplasty is commonly assessed. To my knowledge, such improvements have never been seen in this patient population without surgery or angioplasty. Such improvements don't happen spontaneously, he points out.

Patients were asked to rate pain in the legs at rest before and after therapy. Typically, people with severe atherosclerosis in the legs often experience pain at rest, which also interferes with sleep. Like angina or chest pain, this pain is caused by decreased blood flow. Six of the patients experienced a reduction in rest pain. In 4 of 7 legs, where skin ulcers had formed due to the impaired blood circulation, these healed completely or partially. The time it took to walk a certain distance decreased in all 5 patients studied. Only one study participant had to undergo a leg amputation. When the 39-year-old woman entered the study, she had atherosclerosis in both legs. The front half of one foot was already stained with gangrene, says Isner. In the other leg, the gangrene was already starting in the toes. Gene therapy was performed on both legs and stopped the gangrene in the last affected leg, but failed in the other because it was too advanced, Isner said.

When she came to us she was facing two leg amputations, he adds, without the therapy she would have been amputated on both sides." The amputated leg was the only one in the study whose condition deteriorated. Another woman was also able to prevent an amputation through gene therapy. Only one patient did not improve.

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