Montreal based biotech ExCellThera, founded by study co-senior author Guy Sauvageau, M.D., Ph.D has license to the drug, and armed with an FDA regenerative medicine advanced therapy designation the company is launching new clinical trials in Canada and America involving patients with high risk leukemia.
Stem cells harvested for transplant in blood diseases currently come from the blood itself or from bone marrow mainly, even though cord blood offers advantages. “Although the rate of graft-versus-host disease (GVHD) when using umbilical cord blood stem cells is low, these cells are rarely used because the cords are small and do not contain a sufficient quantity of cells to treat an adult,” explained Sauvageau in a statement.
UM171 was selected after screening a library of small molecules as being the most promising candidate as the drug was previously shown to stimulate the expansion of stem cells from human cord blood in a study which helped to repopulate blood cells for at least 6 months in immunosuppressed mice.
In this study UM171(ECT-001) was used to culture cord blood before infusing it into 22 patients with blood cancers, some had already previous failed attempts at stem cell transplants. When transplanted the UM171 expanded blood cells were observed to establish quickly, none of the patients developed serious chronic GVHD during a median follow up period of 18 months, and despite being high risk only 1 patient died due to treatment related hemorrhage.
“The most impressive result is the low mortality rate associated with UM171 transplantation compared to conventional cord transplantation,” the other co-senior author, Sandra Cohen, Ph.D., said in a statement.
“Not a single patient needed immunosuppression treatment after 13 months, whereas with normal transplants, 50% of patients require such treatment at that point,” Sauvageau added. “No other biotechnology procedure has produced these kinds of results.”
According to the researchers UM171 was revealed to have prompted the stem cells to multiply by an average of 30 fold in only 7 days, and to significantly increase the number of key immune cells in the graft blood such as antigen presenting dendritic cells and mastocytes.
Stem cell transplantation holds great promise for cancer patients, although harvesting cell can be difficult and sometimes complications such as GVHD as well as infections can pose serious risks, which is why scientists are working to find ways to improve the efficiency of the treatment.
Previously programmed cell death was prevented in donated hematopoietic stem cells via blocking BIM and BMF proteins for a short period of time as described in a study published in The Journal of Experimental Medicine.
Another study published in the journal Stem Cell Reports from University of California researchers have found that Viagra can help blood stem cells escape from bone marrow for collection, and showed pairing the drug with a stem cell mobilizer called Mozobil could significantly increase the number of stem cells that enter the bloodstream.
Umbilical cord transplant has the advantage of being available to patients who do not have a matched donor, compared to other transplant methods. UM171 may be able to add some additional benefits such as allowing for rapid and durable engraftment, acceleration of reconstitution of the immune system, and the added plus of a lower mortality rate.
While boosting stem cell counts the candidate can also help to increase the number of usable umbilical cords to be of benefit to even more patients. “While only 5% of umbilical cords are usable when working with the conventional method, our procedure brings that proportion up to 50%,” the researchers noted. “This allows us to increase the availability of genetically compatible transplants by 50% to 80%.”
“We will soon conduct a Phase 3 clinical trial in the hope of obtaining approval from the Food and Drug Administration, which would then make this promising treatment available to the general population as quickly as possible” pointed out Dr. Sauvageau and Dr. Cohen.
