StemCyte's Active Involvement in Research Efforts with Cord Blood Stem Cells
StemCyte launched targeted R&D collaborations with leading researchers and major academic centers to advance our position within cellular therapy. Specifically, we have committed to the following research and development strategies: (1) conduct clinical trials to promote the utilization of its stem cell transplantation products in current FDA-approved indications; (2) develop and clinically validate new transplant indications for its UCB stem cell products and (3) develop innovative regenerative medicine therapeutic indications for our UCB stem cell products.
StemCyte recently participated in a clinical study involving the use of umbilical cord blood to treat a devastating worldwide disease, thalassemia. Thalassemia includes a number of different forms of anemia (red blood cell deficiency), including thalassemia major or Cooley's anemia. The two main types are called alpha and beta thalassemias, depending on which part of an oxygen-carrying protein (called hemoglobin) is lacking in the red blood cells. About 150,000 babies worldwide are born with severe forms of the disease each year. Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry. Recent publications indicate that, with modern supportive therapy, 32% of patients with thalassemia major will die by the age of 35.
After providing donated umbilical cord units to one of the leading research hospitals in Taiwan, StemCyte assisted Dr. T.H. Jiang in investigating the feasibility of using umbilical cord blood transplants from unrelated HLA donors to cure the disease. In the most recent published article, between October 2003 and November 2004, five children with b-thalassemia major received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood transplantation (median dose, 8.8 x 10^7 cells per kilogram of body weight) from unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then evaluated for engraftment, adverse effects and treatment outcome. The median times to neutrophil engraftment, red blood cell transfusion independence and platelet engraftment were 12, 34 and 46 days after transplantation, respectively. This median time of neutrophil engraftment of 12 days in this study is not only faster than that of most published studies of cord blood transplantation, but is also as fast if not faster than most bone marrow or peripheral blood transplants. None of the patients developed extensive chronic graft-versus-host disease as of the date of last contact. All patients were alive at a median follow-up of 303 days after transplantation, with complete donor chimerism and transfusion independence. Chimerism shows that the transplanted stem cells have replaced the patient’s bone marrow.
The study has since been extended to 9 patients, with similar outcomes as reported in an abstract. The engraftment and survival rate of 89% in this small study has been similar to results from related bone marrow transplants for thalassemia.
These results are encouraging and clearly show the feasibility of unrelated umbilical cord blood transplantation in the treatment of children with beta-thalassemia major. StemCyte plans to expand this clinical effort and serve as a worldwide leader by encouraging transplant centers internationally to introduce this therapy early in a patient's life.
Spinal Cord Injury
In February 2008, StemCyte and Rutgers University entered into a research and licensing agreement for a spinal cord injury therapy being developed by Wise Young, M.D., Ph.D., that uses StemCyte’s proprietary human umbilical cord blood (UCB) stem cells in conjunction with lithium.
StemCyte provides financial sponsorship for Dr. Young’s work at Rutgers’ W.M. Keck Center for Collaborative Neuroscience and receive exclusive commercialization rights to the therapy.
Dr. Young’s previous research resulted in the administration of high doses of methylprednisolone within eight hours of an injury becoming the first and only currently available therapy for spinal cord injury. He has now conducted preclinical studies at Rutgers’ Keck Center to determine the growth factor stimulation of stem cells treated with lithium salt. From these studies, Dr. Young concluded that UCB stem cells are the only type of stem cells that, when treated with lithium salt, have a neurotrophic effect that may be used to effectively treat spinal cord injuries. A patent application for his invention has been previously submitted.
In an article by Tim Gilmer, in 2004 Dr. Wise Young and colleagues at Hong Kong University demonstrated that, in rats, lithium stimulates regeneration of the spinal cord and causes stem cells to proliferate. The first in a series of clinical trials, completed in Hong Kong in December 2007, assessed the safety and feasibility of giving lithium for six weeks to 20 human patients with SCI. "It basically showed that the treatment is safe," says Young.
A second double-blind phase II trial, started at the China Rehabilitation Research Center in Beijing, randomized 40 patients to lithium or placebo, to see whether or not the lithium is producing any neurological benefit.
Before this, all 25 centers in the China SCI Network began participating in an observational trial where each center collects data on 20 patients according to protocol, examining the patients in exactly the same way. Since 25 centers are involved and some collect data from more than 20 patients, about 600 patients will have been examined at least three times and followed for a period of one year. "These patients will become the candidates for the phase III trial that will start probably at the end of 2008," says Young. "These are all chronic [long term] SCI patients. Our initial approach is toward chronic patients."
The network also has completed a cell transplant phase I trial involving 30 patients with acute and early SCI. "We operated on the patients, but did not transplant any cells," says Young. [In phase I] we did decompression of the spinal cords of patients between two days and 69 days after injury. We opened up the dura, we exposed the spinal cord, and we also cut into the spinal cord itself — if we thought there was necrotic or broken-down tissue in the middle — to wash out the dead tissue. These patients actually did very well with this procedure. Many of the patients walked, and we just submitted this for publication."
The next study will involve 40 patients and transplantation of umbilical cord blood cells. "These cells will contain most of the stem cells in umbilical cord blood. Blood is damaging to the spinal cord," says Young, "so you have to isolate them, and we're isolating one particular faction of cells called mononuclear cells." These cells will be transplanted into the 40 patients, with half getting a single bolus dose of methylprednisolone. "We have seen in animal studies that a single bolus dose of methylprednisolone — which is the standard therapy for acute SCI — given intravenously, markedly improved the survival of transplanted cells, and we want to see whether this is true in humans.
"So we're going to do what we call a phase two umbilical cord blood mononuclear cell transplant. Once we have completed all these things, the phase I and the phase II, then we're going to take 400 of the patients that have been examined in the observational study, and all of these patients will get umbilical cord blood mononuclear cells — half of them will get lithium, the other half will not. It's a randomized trial to assess the effect of lithium on the umbilical cord blood cells."
What will be learned by this series of studies?
"We now know lithium is safe," says Young. "By the end of the trials we will know whether umbilical cord blood mononuclear cell transplants into the spinal cord are safe. We will also be able to know whether or not it improves function, compared to before the surgery. If we see improved function, we still may not necessarily know that this is directly from the transplant itself. On the other hand, if we see that lithium improves the effect, it must be that lithium plus the cell transplants is better than the transplant by itself," he says. "This, on its own, would be sufficient for us to recommend that the lithium plus umbilical cord blood cells be used for treatment of SCI.
"On the other hand, if we find that umbilical cord blood mononuclear cells don't do anything for people with SCI — they don't improve or even get worse — we would be able to say definitively that this procedure should not be used."