Critical Limb Ischemia or CLI is the culmination of a condition s degenerative disorder called peripheral artery disease (PAD). PAD results from the obstruction of blood vessels, and the most common cases of PAD occur in the blood vessels in the legs. The symptoms are leg pain, difficulty in walking, progressive tissue damage and death, which leads to a need to amputate the limb in order to prevent the onset of gangrene. The best way to treat PAD create new blood vessels that can deliver blood to the tissues of the leg, which will keep the leg tissue alive and prevent cell death and limb degeneration.
To this end, an Israeli stem cell therapy company called “Pluristem” has completed a Phase I clinical trial for its PLX-1 stem cell line as treatment for critical limb ischemia. This phase 1 trial continued for 12 months and was conducted under protocols approved by the United States Food & Drug Administration (FDA), and the German Paul-Ehrlich-Institute. In order for such a clinical trial to be considered significant, the treatment must enhance the percentage of patients who survive without suffering amputation of the affected limb. This endpoint is called the amputation free survival or AFS rate.
Based on the AFS rate after 12 months of treatment, the clinicians involved in the study concluded that PLX-PAD cells seem to provide effective treatment for CLI. Edwin Horwitz, president of the International Society for Cellular Therapy and chairman of Pluristem’s Scientific Advisory Board, stated: “AFS is the single most important endpoint in CLI clinical trials… Even though these Phase I trials were not controlled studies, the data collected in these trials on AFS indicate significant potential for PLX-PAD cells in treating CLI patients.” Because Phase I studies are designed to test the safety of the treatment, they cannot be used to determine the efficacy of the treatment. The PLX-1 cells are definitely safe for human patients, since the study met all endpoints and did not have to be stopped because of unforeseen side effects. Therefore, Pluristem will almost certainly be allowed to conduct Phase II studies with PLX-1 cells, which are designed to determine the efficacy of treatments.
PLX-1 cells are derived from human placenta. Human placenta contains a wealth of stem cells, and one of the stem cell populations in human placenta is a mesenchymal stem cell that can form blood vessels and stimulate the regenerative effects of other stem cells. These particular mesenchymal stem cells derived from placenta can potentially enhance the capabilities of umbilical blood-making stem cells when such cells are used to reconstitute the bone marrow of human patients (see Prather, Toren, Meiron, Expert Opin Biol Ther.2008;8(8):1241-50). Furthermore, these same PLX-1 cells restore blood flow in laboratory animals that suffer from CLI (Prather, et al., Cytotherapy. 2009;11(4):427-34).
Since the only present cure for CLI is amputation of the affected limb, regenerative treatments like PLX-1 are a welcome site for those who suffer from Peripheral Artery Disease.