Posted by Sharyn S. on February 21, 1999 at 03:34:53:
The following notation is from this address:
www.diabetes.com/FEATURES/FST10039.HTM
Far down it does make mention of xenotransplantation-
More and More I feel the cure is close irregardless
of the fact that tangible evidence isn't in my grasp-
(at-this-moment). Why do we feel frustrated? Because
inside we KNOW it's CUREABLE! Please read the following:
What does the 21st century hold for diabetics? In this
occasional series Diabetes.com examines the frontiers of diabetes. Today:
Do islet cell transplants hold the key to a cure?
After 30 years as a type 1, insulin-injecting diabetic, Don Smith knows how it feels to live in a world without diabetes. In 1993, Smith had 1.6 million insulin-pumping islet cells squirted into his pancreas in a St. Louis operating room and has lived injection-free ever since.
"The operation has totally changed my life," says Smith, 39, in an easy-going Arkansas drawl, adding that he can now enjoy life's simple pleasures, such as eating his beloved chocolate-covered cherries whenever he wants to.
The transplant operation was performed at Washington University in St.Louis by Dr. Paul E. Lacy, one of the world's foremost experts on islet cell transplantation. Over the years, he has performed the experimental procedure on a total of 17 diabetics. Of these, 13 have been able to substantially reduce the amount of insulin they required, and four have been able to kiss insulin injection good-bye. Eventually, however, all but one had
to resume insulin shots. That person is Don Smith. To this day neither Lacy nor anyone else knows why.
Smith is probably the most successful islet-cell transplant recipient in the world, and he has become a talisman of hope for researchers and diabetics alike. When his story appears in a newspaper or magazine, as it often does, Smith gets swamped with calls and letters asking him for more information, or, in some cases, to heal them. "It's kind of weird," he admits.
But Smith's story is at best a cautionary tale. While it shows how tantalizingly close researchers may be to finding a cure for diabetes using transplanted islet cells, it also underscores how far they have to go. Smith knows this too well. In early 1997, fours years after he received his transplanted islet cells, they have begun to poop out, producing less and less insulin. "I'm still not a diabetic yet," he explains. "But I'm a lot closer
than I was."
***
Islet cells are found inside the pancreas, and in a healthy person they control blood sugar by reading the level of glucose in the blood and churning out more insulin when blood sugar runs high, or less when glucose is low. But in a person with type 1 diabetes, something goes wrong with this cycle. Scientists have yet to piece together all the details but they know that diabetics are essentially victims of friendly fire:
Their immune systems somehow mistake their islet cells for germs and destroy them. Scientists have been investigating the possibility of islet cell transplants as a cure for diabetes since the 1960s. The idea sounds tantalizingly simple:
Replace dead islets with fresh ones harvested from human cadavers and--voila!--no more diabetes. But putting this into practice has proven maddeningly difficult. Three hundred islet cell transplants have been performed since 1974, none have been able to permanently restore normal insulin production.
To make islet cell transplantation a realistic therapy for the more than 700,000 Americans with type 1 diabetes, scientists must solve several complex biological puzzles. One of the most fundamental is how to sidestep the immune system, the complex biological defense system designed to attack and destroy all foreign invaders, be they bacteria,viruses--or transplanted islet cells. Until now, restraining the immune system has required powerfulimmune-suppressing drugs. The problem with these drugs is that they leave the body susceptible to all sorts of infections and some cancers. For thatreason, researchers have performed most experimental islet cell transplants only on diabetics who also needed new kidneys and would require
immunosuppressants anyway. That was the case with Smith.
deally, of course, islet cell transplantation shouldn't suppress the immune system. That's why researchers have been investigating new ways to protect transplanted islet cells from immune system attack without the use of dangerous immunosuppressants. Currently three of the most popular
approaches include microencapsulation, bone marrow transplants, and gene therapy.
Microencapusulation.
Several universities and small biotechnology companies around the country are working to develop tiny protective containers to shield the delicate islet cells from the immune system. These microcapsules, as they are called,contain tiny pores that allow insulin, glucose, oxygen and other molecules to pass back and forth but are still small enough to block the much larger
killer cells of the immune system.
VivoRx, of Santa Monica, is a leader in microencapsulation
research. In 1993, the company was the first to show that microencapsulated islet cells could work in humans using human islets protected inside microcapsules made from a seaweed-derived material. Also working on this method are
Neocrin Laboratories and academic labs such as the Joslin Diabetes Center in Boston and the Diabetes Research Institute at the University of Miami.
Microencapsulation looks promising, but there are still significant problems to be solved. While each microcapsule is only as wide as a human hair, several hundred thousand are needed to control human blood sugar, and they take up too much space. Researchers are working on ways to make them more compact. Another problem is that the islets gradually give out
and must be replaced every six months or so, so at present, the procedure is only a temporary solution at best.
Bone Marrow Transplants
Researchers at the world-renowned Diabetes Research Institute in Miami this month plan to kick off a pioneering clinical trial to investigate whether transplanting islet cells and bone marrow taken from the donor can trick the recipient's immune system into accepting the new islets. What does bone marrow have to do with islet cells? A great deal. The cells of the immune system originate in the bone marrow. Scientists hope that marrow from the islet cell donor can "re-educate" the recipient's immune system to accept the foreign islets as their own.
In the study, patients are scheduled to take immunosuppressant drugs at first to give the transplanted bone marrow and islet cells a chance to settle in. Then the drugs will be gradually withdrawn. If all goes well, a year after their transplants, islet cell-marrow recipients should be off the immunosuppressants altogether.
Gene Therapy
Gene therapy is based on research showing that as cells of the immune system patrol the bloodstream, they determine whether cells they encounter are friend or foe by certain proteins attached to their surfaces. If researchers were able to tweak the genes in the donor islet cells to make their surface proteins recognizable as "friend" to the recipient's immune
system, the new islet cells just might be left alone.
Preliminary animal studies have shown that this idea works, no one knows if it works in humans, at least not yet.
The Supply Problem
There's one more major question researchers must answer before islet cell transplantation can become a treatment for the masses: Where will doctors get enough of them? Only 7,000 to 9,000 bodies are donated for organ transplants each year in the United States, too few to supply islet cells for more a tiny fraction of the half-million Americans with type 1 diabetes. To
solve the supply problem, researchers are looking to pigs. Their organs closely resemble our own. And some lines of pig have been genetically engineered to carry key human genes that make their organs look nearly human to a recipient's immune system--and, therefore, less likely to be rejected.
Recently, two small but provocative studies have shown this strategy can work. Last year Dr. Anthony Sun at the University of Toronto reported inthe Journal of Clinical Investigation the first successful transplant of islet cells from pigs into insulin-dependent monkeys. The monkeys accepted the cells
and went on to achieve normal blood sugar control.
A few months later, Dr. Robert Elliott of the Auckland School of medicine in New Zealand successfully transplanted pig islet cells into two human diabetics. The cells, says Elliott, only produce about a quarter of each patient's insulin requirements. What's most interesting about the study is that while one of the test subjects had a kidney transplant and takes immunosuppressant drugs, the other had only the cell transplant and takes no immunosuppressants.
Still, xenotransplantation, as the procedure is called ("xeno" means "foreign") remains controversial. Although pigs used for transplantation are raised in a sterile, disease-free environment, critics worry that their cells might transmit diseases to their new hosts. Just last month, researchers at
London's Institute of Cancer Research reported that a virus found in pig cells had crossed over and infected human
cells--an event doctors had thought unlikely. As a result, Britain and a few other countries have declared a moratorium on xenotransplants.
Of course, proponents of the procedure argue that such fears are
unfounded and that pigs could supply a safe and limitless supply of islet cells and other transplant organs. So far the Food & Drug Administration seems to agree: The agency has approved xenotransplant research, but requires strict monitoring of tissues, organs, and recipients. ***
How close are we to a diabetes cure using transplanted islet cells? Most researchers are reluctant to speculate. Some think the procedure might be perfected within the next few years. Others say it will take much longer. In the meantime diabetics like Smith continue to wait.
These days, Smith and his doctors are planning for his eventual return to the world of diabetes. "Nobody's walked on this ground before, so we're trying to figure out what to do," he says, adding that he soon may have to start taking oral diabetes drugs prescribed for people with type II diabetes.
Despite the looming failure of his islet cell transplant, Smith is anything but discouraged. "I have a diabetic son," says Smith, "and I'm proud to be part of the research aimed at finding a cure for kids like him. I don't want my
son to have to go through what I've endured--loss of eyesight and kidney failure."
When diabetics around the country seek him out as a harbinger of a coming cure, Smith updates them on the progress--and problems--of islet cell transplantation. Then he tells them what to do in the meantime--practice tight control: "I had an 84-year-old lady call me up saying she wanted me to cure her," Smith recalls. "I said, 'Ma'am if you just
take care of your diabetes, eat what you're supposed to, exercise, and keep your blood sugar in the normal range, you'll live to be 110.' You know what? She was real happy to hear that."