The name is not commonly known and is difficult to pronounce, but the disease afflicts an estimated 12 million Americans. It’s called critical limb ischemia. Treatments are lacking and often require amputation, but help may be on the way: A potential solution for people afflicted with diabetes and obesity who are facing amputation of a limb due to circulatory problems caused by ischemia is soon to begin clinical testing at Duke University.
The disease causes narrowing and hardening of arteries, thus reducing blood flow. If not treated, victims can suffer nerve and tissue damage. The disease can also trigger gangrene, which often requires amputation.
In lab tests on animals, the use of stem cells not only improved blood flow, but also grew new blood vessels. Dr. Chris Kontos, co-director of the Duke Heart and Vascular Group, will be coordinating the trial that focuses on the stem cell regime developed by Pluristem Therapeutics.
But these are not embryonic stem cells, which have created so much controversy within the medical community. Rather, Pluristem, an Israeli biotherapeutics company whose stock is traded on the Nasdaq, is pioneering the use of stem cells derived from the placenta.
“There is no good medical therapy for critical ischemia,” said Dr. William Prather, who is a consultant with Pluristem and helped pick Duke as one of the sites for the test. “There are surgical therapies that can clean out the vessels, but there is no medication or procedure to grow new blood vessels around the obstruction. That is what we have proved in animals.”
Duke is currently enrolling subjects for the trials for the Phase I tests of Pluristem’s PLX-PAD solution. A similar trial will take place in Alabama. “Both locations have used other companies’ cells in the past, so they are familiar with stem cell therapy,” Prather said.
Pluristem is working on a variety of products that would enable stem cell transplants between unrelated donors and patients. The concept is called allogeneic, or “taken from different individuals.” The company wants to treat both severe ischemic and autoimmune disorders; it recently received funding support from the Israeli government.
The Pluristem method is not the first to use stem cells as a potential treatment for ischemia, Prather pointed out. However, the other choice is stem cells taken from bone marrow. Placenta cells are much more widely available, less expensive and don’t require donors to go through the surgical process to extract cells from the hip.
“We don’t have to do any of that with our cells,” Prather explained. “Our cells come off the shelf, they are one size fit all, they come from material that is thrown away, and outpatients can be injected in a process that takes 30 minutes. They are observed for six hours and then sent home.”
In late July, the first patient was injected with the proposed treatment in a clinical trial in Germany being run in parallel with the US tests. As many as 12 patients will be injected, with a mix of smokers, diabetics and obese subjects to be tested in the US.
Phase I trials focus on safety. If the treatment is found to be safe, Phase II trials would begin. The US Food and Drug Administration granted Pluristem approval for the Phase I trials earlier this year.
The treatment is intended for victims of “late stage” ischemia who have not responded to other treatments or surgery and face the prospect of amputation. People selected for the trial will already have a condition related to ischemia, such as an ulcer or nerve pain.
All test patients will receive one injection and half will receive a second, Prather said. There will be no placebos. Pluristem will track both safety and efficacy data over a three-month period following the injections. Although the primary “end point,” or goal of the Phase I trial, is safety, Prather said doctors also will be able to track whether the patients show improvement.
“In animal trials, we saw improvement in blood flow in about three weeks,” Prather explained. “I’m not sure we can equate that to three weeks in humans, though. We could get efficacy in blood flow within a month or two months of injection.”
Even if the treatment proves safe and ultimately is granted FDA approval for sale, Prather pointed out the healing process would not be a quick one. “If these cells are going to be effective, blood flow improvement will be a matter of weeks and months, not inject today and improve tomorrow,” he said. “It just takes time for a new blood vessel to grow.”
Duke and Pluristem agreed to partner on the trial after Pluristem came in contact with Dr. Brian Annex, a former physician at Duke. “He is a world-renowned leader in angiogenesis (the growth of new blood vessels),” Prather said. “He was in transition at the time when we talked last year, and he recommended that we work with Dr. Kontos. Annex later joined the Pluristem Scientific Advisory Board.
“We are very excited about the possibilities,” said Kontos, who hopes for the first patient injections to be made by the end of August.