Feature
New Hope for PAD Patients
December 21, 2006
Stem cell trial offers hope for patients suffering from peripheral artery disease
Michael Murphy, an assistant professor of surgery at Indiana University School of Medicine, and his colleagues at the Indiana Center for Vascular Biology and Medicine are conducting a unique clinical trial that's offering hope to thousands who suffer from peripheral artery disease (PAD).
When she began feeling pain in her left foot in mid-2005, Adriane Pruitt feared the worst.
Five years before, Pruitt had started suffering severe pain in her right foot. Not just an ache, this was pain that eventually left her hospitalized and treated with major pain killers. Eventually, her pain was diagnosed as a circulation problem, but not before her toes were amputated. In the end, doctors resorted to artery bypass surgery that left her leg seriously scarred.
Another such surgery, and more scarring, seemed to be ahead when Pruitt was referred to Dr. Michael Murphy, an assistant professor of surgery at Indiana University School of Medicine who is testing a new approach to treating such circulation problems.
With funding from Biomet Corp., Murphy and his colleagues at the Indiana Center for Vascular Biology and Medicine are conducting a unique clinical trial using stem cell injections as a treatment that could offer hope to tens of thousands of people who face sores, ulcers, and even amputations due to severe peripheral artery disease (PAD).
Using adult stem cells extracted from patients' own bone marrow, Murphy injects the cells into the patients' legs where the circulation problems exist. If his research premise is correct, the stem cells will stimulate the growth of new blood vessels in the leg, improving circulation.
After a clinical trial to treat her PAD, 23-year-old Adriane Pruitt's pain subsided and eventually disappeared. "My life depended on this," said Pruitt.
Pruitt, a 23-year-old Indianapolis resident, underwent the treatment in September 2005. By November, the pain was beginning to subside, she said. By the first of the new year, it was gone. She said she gratefully told Murphy, "My life depended on this."
While he appreciates such enthusiasm, Murphy is cautious. This is a small, initial test, and he knows it can take a long time to fully test a new treatment's effectiveness and safety for large numbers of people. "Over the next five years these kinds of trials will determine if the procedure is effective in treating cardiovascular diseases, and which stem cells populations are best," Murphy said.
Nevertheless, Murphy is pleased with the results from the first 15 patients treated. The experiment was what's called a phase 1 trial. Such initial experiments generally involve a small number of patients to provide an initial test of the safety of a new procedure or drug. So far, Murphy said, "It seems to be a very safe procedure."
As for effectiveness, "A significant number of patients responded, some very well,” he said. “We're still gathering data to determine who responded and why."
While Murphy is appropriately cautious about the results from a small trial, he knows there is nothing small about the need. About 10 million Americans are affected by the poor blood circulation—generally in the legs—of peripheral artery disease. It is caused by atherosclerosis, the clogging and hardening of arteries that can lead to heart attacks. Although about half of those with PAD have no symptoms, others report varying levels of pain and other symptoms including numbness and sores on the legs and feet.
Early treatment often is similar to actions to prevent heart disease, such as a better diet, stopping smoking, losing weight, and, if appropriate, cholesterol-lowering drugs. If the disease progresses, patients may receive an artery bypass graft or an angioplasty procedure that widens the blood vessel.
"But as many as 12 percent of these patients are not able to have such surgery, and 30,000 to 50,000 people in the United States receive amputations annually due to PAD," said Murphy. For many of these severely affected patients, their quality of life is similar to patients battling terminal cancer, he says.
The cells used in the IU trial include adult stem cells, which are "parent" cells that can create new specialized cells when needed by the body. In the IU trial, researchers are using stem cells—and slightly more specialized descendants called progenitor cells—that can create the cells that make up the lining of blood vessels (not embryonic stem cells whose use is controversial).
For the procedure, Murphy extracts bone marrow from the patient's hip while the patient is under a general anesthetic. The adult stem cells and progenitor cells are separated from the bone marrow in a laboratory procedure while the patient recovers from the anesthesia. Later, the cells are injected into the patient's leg.
The hope is that the injected cells will stimulate the production of blood vessels that will bring new circulation to the affected tissues. Previous studies in animals and other laboratory tests indicated that the injections of the stem and progenitor cells had such an effect, prompting the human trials.
So while the it's too early to judge the results, "We think this is a very promising treatment that could help patients with severe peripheral artery disease for whom there is now no effective therapy, " Murphy said.
Next, Murphy and his colleagues expect to take two routes in hopes of improving the procedure. The first one is to team up with a North Carolina company, Aldagen Corp., which is developing techniques to identify and separate the stem and progenitor cells that are more likely to promote blood vessel growth. In the second, they will test equipment that will shorten the time necessary to extract stem cells from bone marrow to 20 minutes, instead of the five hours necessary now.
In the future, Murphy and his colleagues hope to conduct trials using cells taken from fat tissue and from umbilical cord blood to avoid the surgery necessary for bone marrow extraction. Research also is under way to determine whether the cells could be modified in ways to encourage them to produce more growth-enhancing proteins before they are given to the patients.
In the meantime, Adrian Pruitt is enjoying the relief from pain that she experienced after participating in the clinical trial using stem cells to treat peripheral artery disease. And Murphy hopes that continuing research and new treatments with stem cells will bring relief to millions of others who suffer from PAD.
