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For 15 years, Alberto Hayek, MD, has been conducting research on islet transplants, while also treating children with diabetes and teaching pediatric endocrinology at San Diego's Children's Hospital. Born in Colombia and educated at Yale and Harvard, Dr. Hayek is currently the lead investigator on islet cell transplantation at the Whittier Institute of La Jolla, California.
"When I first began, diabetes wasn't even considered an endocrine disease." reflects Dr. Hayek. "A trip to the clinic was punishment. It was thought all diabetics needed to do was watch their diet and inject insulin. We now know how much more complicated diabetes is."
Dr. Hayek is particularly concerned about children with diabetes. "We've seen the terrible price our children have paid for our misconceptions," he said. Indeed, the incidence of diabetes in children is higher than any other chronic illness, including multiple sclerosis, cystic fibrosis and muscular dystrophy. Even more unsettling is the fact that type 1 diabetes in children between the ages of one and five is increasing by an alarming rate of 10 percent a year. Fortunately, there is hope for the future.
The State of the Art
Organ transplants in people with diabetes have a reported 85 percent success rate in curing diabetes and a 98 percent survival rate for the patient. Today, individuals with diabetes who are in need of a new kidney and will receive a transplant are also advised to receive the complementary pancreas, since it offers them the chance to cure their diabetes.
However, this is still major surgery and is not undertaken lightly. Powerful immune suppression drugs are given to reduce the likelihood that the body will reject the new organs. The side effects of these drugs are often severe. Still another obstacle is the shortage of donor organs. On average, only 2,000 suitable organs are retrieved in time for transplant each year.
In special cases, a partial pancreas transplant may be performed. In such procedures, half of the pancreas is removed from a living relative and is transplanted into the individual with diabetes. While such a partial transplant can overcome the problem of finding a donor, the results are not as successful as whole-organ transplants. The removal of half the pancreas can also cause diabetes in the donor.
Dr. Hayek believes the cure for diabetes lies with transplanting islet cells, which are the cells in the pancreas that produce and modulate insulin. In the early 1960s, researchers successfully harvested islet cells, transplanted them into rats with anti-rejection drugs and cured diabetes. Unfortunately, the procedure's success rate in humans has been extremely low, with 90 percent of the patients still requiring some form of insulin therapy.
So why is Dr. Hayek so optimistic? "The current skepticism about islet cell research is understandable," Dr. Hayek states. "Early success led to a massive media blitz, including claims of a cure. When a cure didn't come as quickly as expected, people began to lose faith in the research. However, steady advances continue to be made, and I truly believe a cure is possible."
Two obstacles must be overcome to make islet cell transplantation a viable option for curing diabetes in large numbers of individuals. First, the number of islet cells available for transplantation must be increased. Teaching immature cells to produce insulin has been at the core of Dr. Hayek's efforts. In collaboration with Drs. Gillian Beattie and Fred Levine at the University of California, San Diego, Dr. Hayek has achieved recent success in getting islet cells to multiply. Unfortunately, as the cells proliferate, they seem to lose their ability to produce insulin.
A more promising option may be the possibility of obtaining stem cells from fetal tissue. Stem cells are young cells that have not yet become specialized. If stem cells can be taught to multiply and produce insulin, we will have an unending supply of new islet cells that can be grown in the lab, eliminating the need for donor tissue.
The second obstacle is the rejection of the transplanted cells. The body recognizes the new cells as foreign and destroys them. One approach is to protect the islet cells by isolating them in capsules. The problem with this strategy is that the capsules degrade, so it requires a large number of cells for the transplant to be successful.
Anti-rejection drugs can help protect the new cells but often produce dangerous side effects, making them a bad choice for young children. Nevertheless, Dr. Hayek does not believe that transplants will ever be performed successfully without immune suppression. "You not only have to overcome the body's natural tendency to reject the donor organs or cells, you also have to somehow block the patient's auto-immune response, which caused the diabetes in the first place."
The search for an anti-rejection drug that reduces or eliminates side effects may be at an end. At the University of Miami, researchers Camillo Ricordi, MD, and Norma S. Kenyon, MD, are using a new blocking antibody, in conjunction with islet cell transplantation, on a group of rhesus monkeys. After injection of islet cells into the liver along with the blocking antibody, the monkeys have remained free of diabetes for over one year. The transplanted islet cells are functioning normally, and the monkeys are showing no side effects from the new drug.
It is unclear yet whether the blocking antibody can eventually be discontinued without rejection of the transplant. There is some evidence that the body builds up a tolerance to the implant, and the need for immune suppression may not be permanent.
Dr. Hayek is quick to point out that these monkeys are surgically diabetic. That is, they have had their pancreases removed to artificially create diabetes. The monkeys do not have the auto-immune response present in type 1 individuals. The real test will come when trials begin on humans to see if the new drug is successful in overcoming both types of rejection. Dr. Hayek may soon begin a clinical trial that will test the antibody-blocking drug on adult type 1 individuals. The trial is tentatively scheduled to begin early next year.
There are many challenges ahead if islet cell transplantation is to be successful. As each question is answered, new ones are created, but Dr. Hayek is not giving up. "The first kidney transplants were a complete failure. Now they are our most viable treatment option. Islet cell transplantation and genetic engineering are in their infancy. We're not giving up until a cure for diabetes is found."
To find out more about Dr. Hayek's research or to obtain information about the Whittier Institute, write to: Whittier Institute for Diabetes, 9894 Genesee Avenue, La Jolla, CA 92037.
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