Jewish World Review March 4, 2003 / 30 Adar I, 5763

An artificial bacteria could save your legs

By Ed Susman | Scientists are convinced that someday they will learn how to harness the burgeoning knowledge in human genetics that will allow them to solve some of the world's most difficult medical problems. Researchers appear to be able to isolate and replicate the genes required to combat disease or overcome genetic dysfunction -- but a major roadblock has been a technique to safely get the gene to the right place in the body without causing other damage.

Doctors now think that they may have found one solution: Create an artificial bacteria that contains the "knowledge'' that Nature gave the microorganism so that it can attach itself to the cell wall. But don't create for it the potency to inflict other damage.

The result of these early experimentations might save your legs someday.

Anthony Comerota, M.D., director of the Jobst Vascular Center in Toledo, Ohio, reported at a cutting-edge scientific meeting in Miami Beach, Fla., that early studies with a synthetic bacteria appears to speed healing in the legs of patients in danger of requiring amputation.

The synthetic bacteria contains within it a gene that, when expressed in humans, begins a cascade of molecular events that encourages growth of blood vessels.

"When more blood gets to the wound, healing can occur more quickly,'' said Comerota at the 15th International Symposium on Endovascular Therapy.

The procedure, known as therapeutic angiogenesis -- the generation of new blood vessels -- is designed to enhance formation of small blood vessels by using the growth factors that regulate cell division and tissue proliferation. When injected into thigh and other leg muscles, the genetically engineered bacteria interacts with the cells that line blood-vessel walls, integrates itself into the nucleus of those cells and directs cells to grow new blood vessels.

Comerota reported that in a preliminary safety study involving 51 individuals, the injection of the bacteria with the angiogenesis gene caused none of them to suffer serious adverse effects.

The only unwarranted side effects among a few patients was soreness at the site when the "non-viral fibroblast growth factor'' was injected. The injection was made into leg muscles close to the area where the wound was not healing properly. Comerota said such wounds occur when leg arteries become blocked due to hardening of the arteries or other factors that reduce blood circulation to the area.

Although the initial study was just to determine if giving the bacteria was safe, "these people reported less pain, their ulcers healed faster, and their blood pressure was better after six months of treatment,'' said Comerota, who is also a professor of surgery at the University of Michigan in Ann Arbor.

The doctors were especially wary of whether causing angiogenesis in the leg might also cause inappropriate blood-vessel growth elsewhere, such as in the eyes, where adding blood vessel growth can cause a blinding disease known as macular degeneration. In patients with cancer, angiogenesis can encourage and stimulate tumors. In fact, numerous scientists are working on ways to prevent blood-vessel growth in tumors, or "anti-angiogenesis.''

Comerota said doctors were pleased that they could find little evidence that the genetic material migrated throughout the body -- only minute amounts could be detected in the urine of one patient. He also said he could find no evidence that the human body made antibodies to the bacteria -- meaning that subsequent treatment would be possible with triggering an immune system attack on the therapeutic agents.

When looking at the first trial, Comerota said leg pain levels declined significantly among the patients between eight to 24 weeks of treatment; in one patient, the ulcer that had threatened the need for amputation healed completely.

Overall 68 percent of the surface area of the wounds healed at the end of the study. "That increased to 80 percent after a year,'' Comerota said. There were also significant increases in blood pressure in the legs after eight and 12 weeks, but Comerota said those improvements in blood pressure, while encouraging among people whose blood flow in the legs was compromised, might not be medically meaningful.

The successful first stage studies, being reported by Comerota, have led to plans for a second, larger study that will compare patients receiving the experimental product with those who receive a sham or placebo treatment. The studies are supported by Gencell, a subsidiary of the pharmaceutical giant Aventis, he said.

"Despite recent problems with gene therapy, the strategy of molecular engineering remains a great promise for people with serious, difficult-to-treat wounds,'' said Barry Katzen, M.D., founder and medical director of the Miami Cardiac & Vascular Institute. "It still makes a lot of sense to use a genetics approach in treating these diseases. But it has to be done carefully.''

Katzen said unsuccessful wound healing due to circulatory problems in the legs is a difficult problem to treat. "Those people are at risk of losing their legs,'' he added. "It affects a lot of people.''

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