News Release

Islet cells from swine reverse insulin dependency in diabetic non-human primates

Researchers achieve best survival to date with no evidence of antibody-mediated rejection

Peer-Reviewed Publication

S. Hayes Consulting

June 3, 2003 – Washington, DC: Today at the American Transplant Congress, Martin N Wijkstrom, M.D., on behalf of researchers from the Diabetes Institute for Immunology and Transplantation, Department of Surgery at the University of Minnesota and Immerge BioTherapeutics, Inc., presented data showing reversal of diabetes in monkeys after transplantation with porcine islet cells. Immediately post-transplant, each of the monkeys no longer required insulin and achieved normal glucose levels. Researchers used combinations of immunosuppressive therapies to allow the cells to function within the primates for more than 70 days.

"This data is very significant because while we have been able to reverse diabetes in past islet studies, we had only seen 2-3 week survival times before the graft was lost due to the overwhelming rejection response," said Professor Bernhard Hering, M.D., Associate Director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota. "For this study, we looked at immunosuppressive regimens that were well tolerated in past monkey-to-monkey islet transplants. The survival times we are reporting on today should only increase as we further optimize the immunosuppressive regimens."

In this study, diabetic cynomolgus monkeys were transplanted with islets purified from the pancreas of adult pigs or miniature swine. They were then treated with an immunosuppressive cocktail, including induction and maintenance therapy. All animals became insulin independent and reached normal glucose levels in the period after transplantation, and a number of animals were insulin-free for up to 70 days after transplantation.

"None of the animals showed evidence of antibody-mediated rejection, which is a major type of rejection for solid organs like kidneys and heart" said Henk-Jan Schuurman, Ph.D., Vice President Research at Immerge BioTherapeutics, Inc. "The immune rejection responses we did observe were T-cell mediated as we would see in allo-transplantation. This is extremely encouraging because we have a great deal of experience in managing this type of response with medication in human-to-human transplants."

Because of the risks associated with immunosuppressive medication, at present, islet transplants hold the greatest promise for a small subset of diabetics (approximately 1%), known as "brittle diabetics." The brittle diabetic patient has blood glucose levels that "over-react" to minute changes in diet, exercise and/or insulin. Although small in number, these patients are of great concern because they are not well controlled by insulin and experience poor quality of life with multiple hospital admissions.

"We are looking at both islet and solid organs for potential xenotransplantation from the strain of miniature swine we are developing and are currently engaged in pre-clinical trials in both areas," said Julia Greenstein, Ph.D., CEO and President, Immerge BioTherapeutics, Inc. "In this swine, we have been able to "knock-out" the gene that is responsible for beginning the immediate and overwhelming rejection process that happens in transplants between species. In addition to the genetic modifications and the size of the animal, which is appropriate for human transplant, our safety research shows that cells from this line of pigs, in contrast to most other cells tested, don't have the capacity to spread porcine endogenous retrovirus to human cells in culture."

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The study was funded by Immerge BioTherapeutics, Inc. Immerge BioTherapeutics was formed on September 26, 2000, as a joint venture between Novartis Pharma AG and BioTransplant Incorporated. The company, which began operations in January 2001, focuses its research efforts toward developing therapeutic applications for xenotransplantation. The name of the company derives from its use of immunology to address the challenges of conducting transplants between species.


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