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DRI Research Update

The need to find a method of successful islet transplantation using fewer donor islets and a way to do so without immunosuppression were two of the more important issues discussed at the October 28, 2000 Diabetes Research Institute Foundation Research Update in New York City. Speakers at the seminar included Dr. Camillo Ricordi, Dr. James Shapiro, Dr. Norma S. Kenyon, Dr. Luca Inverardi, and Dr. Kevan Herold.

Dr. Ricordi, the inventor of the device used to extract islets from the pancreas, talked about the history of islet transplantation, describing the first recipients in 1990 as those persons who had had cancer and required a pancreatectomy. They all received a series of anti-rejection drugs that later caused them to have diabetes. He indicated that the lack of available islets is a major hurdle. Patients involved in the Edmonton trials are receiving islets from two donors, while Dr. Ricordi has been giving patients islets from one donor. At this rate, they can treat only 1% of the potential patients. Their goal is to reduce the number of donors needed even further. Dr. Ricordi that he has a patient who has dramatically reduced his insulin dependence with his "new" islets working more efficiently as time progresses.

Displaying slides showing how the less than 1 tsp. of islets are actually extracted from a pancreas, Dr. Shapiro indicated that the procedure of giving the islets to the recipient takes a mere 15 minutes. They are injected through the portal vein into the liver. Most patients are home within 24 hours; one was back at work within 12 hours. Dr. Shapiro emphasized that they had treated only "very brittle" diabetics and that they will not consider children for the trials at this time. His reasoning was the 1% chance of lymphoma from the immunosuppressant drugs. When that chance has been reduced to 0.1% or even 0.01%, they will consider children for the trials. He did not say how much time it might be before this happens. Commenting on the use of living donors, Dr. Shapiro noted that most donors can develop diabetes. So far, none of the 13 participants in his trial have developed side effects. One of the patients has been diabetes-free for 20 months. Three of the patients required "some" insulin during mild illnesses.

Dr. Norma S. Kenyon, whose 8 yr. old daughter has diabetes, is involved in the study of dogs and monkeys, using various procedures, such as radiation of the islets, to prevent graft rejection. She discussed the pancreactectomies of monkeys who were then given five doses of Anti-CD154. After monitoring their blood glucose for a year, during which they were given immunosuppressant drugs, they then survived for 3-5 months without the drugs. Then, they rejected the grafts. At this time, Dr. Kenyon is focusing on "Hematopoietic Chimerism," the coexistence of donor and recipient immune cells in the recipient's body. One of the goals is the transplantation of bone marrow, anti-CD154 and short term immunosuppressants. She indicated that chimerism and grafts have been successful in dogs.

The "Challenges of Islet Supply" were discussed by Dr. Inverardi. He noted several ways to do solve this problem: increase the pool of human donors; increase the viability of beta cells and their resistance to damage; genetically engineer insulin producing cells; expand human beta cells in vitro; generate insulin producing cells from stem cells; or use non-human organs. Obviously, each of these alternatives have their own problems, but he seemed somewhat optimistic about the use of stem cells, some of which exist in adults. Dr. Inverardi pointed out that they have learned that muscle cells can produce blood cells; previously, the experts believed that bone marrow cells were the only cells capable of doing this. However, they need to understand how to teach "stem" cells to differentiate into beta cells and how to prevent the recurrence of autoimmunity. With respect to non-human donors, Dr. Inverardi mentioned the problems of rejection and disease transmission, both zoonoses like anthrax and rabies and PERV (Porcine Endogenous Retro-Virus) transmission, the transmission of what are innocent viruses in the donor to the recipient where the virus can be harmful.

In another trial, Dr. Kevan Herold has been giving patients "Ala-Ala," a monoclonal antibody that binds to the CD3 on human T cells. Out of 12 patients, 75% have have increased insulin production. After 6 months, their bodies were producing even more insulin and he expected this trend to continue. He noted that the University of Minnesota was using this same antibody with islet transplants and the results were promising.

Finally, Dr. Robin Nemery gave a presentation of the use of insulin pumps by children and adolescents. Essentially, she indicated this was the best way to treat diabetes until the cure is found.

Brenda Hitchcock

Posted November 1, 2000

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