Another reason to be an organ donor. -D ______________________ A Cure for Diabetes Who will benefit, and when? by Todd Zwillich Medically reviewed by Dr. Craig H. Kliger Attorney Robert Tesky and high school senior Ryan Dinkgrave have one thing in common that defines their lives: Type 1 diabetes. The difference is Tesky believes he is cured, while Dinkgrave wonders if the new treatment will ever be available to him. For more than a year, Tesky, 54, has lived free of insulin shots. He no longer worries about blacking out from an injection that sends his blood sugar plummeting. He doesn't fret as much about plaque building up in his arteries as a consequence of the disease. His future -- like that of six other Canadian patients who received the experimental new treatment -- holds the promise of health, not the prospect of a kidney transplant. "This has given me a whole new beginning," says Tesky, who months before the treatment underwent two angioplasties to open plaque-clogged arteries to his heart. It's nothing short of a miracle." Tesky and the other Canadians received transplants of islet cells carefully and quickly removed from donor pancreases, then injected into their livers. Those cells now detect his body's blood sugar levels and produce insulin as he needs it. For all practical purposes, he no longer has diabetes. Indeed, when Canadian researchers at the University of Alberta announced their breakthrough in May, scientists with the American Diabetes Association were, for the first time, cautiously using the "C"-word: Cure. The New England Journal of Medicine considered the news so important that it broke its own embargo and announced the study results seven weeks ahead of publication. The National Institutes of Health (NIH) immediately announced a $5-million, 10-city follow-up study to try to duplicate the results. But Ryan Dinkgrave, a student in Livonia, Mich., didn't start celebrating. Not yet. He knew it would be difficult getting enough islet cells for a transplant. He knew there are many hurdles ahead. And he is right. "It would be great to not have to worry about diabetes, but right now I'm not going get too hopeful," says the 17-year-old. Hurdles Lie Ahead Serious problems must be overcome before islet cell transplants can be offered to most of the more than one million Americans with type 1 diabetes -- the harshest form of the disease -- which usually strikes in childhood. Islet cells are fragile, and donated pancreases are rare. Thus, experts say it could be years before this revolutionary procedure is widely available. Islets are actually a group of five different types of cells that work together to monitor glucose (the body's blood sugar), and make insulin, which helps convert glucose into energy. Lakey and his colleagues had to use about two donated pancreases for each patient because so many islet cells were damaged during the harvesting process. Tesky's transplant was even more difficult. He was called to the hospital eight times and underwent three procedures before the treatment worked. "Our program now is really limited by our ability to get [islet] tissue," says Jonathan Lakey, MD, one of the surgeons who treated Tesky and the six other diabetics in Edmonton, Canada. Still, techniques are improving, and within three years Lakey says he expects a 1-to-1 ratio: one donated pancreas to treat one diabetic. A Shortage of Organ Donors But even then, demand will far outstrip the supply of pancreases. The only way to get functioning islet cells is from people who died after agreeing to donate their organs. And that equation doesn't add up to broad success: Only about 6,000 people a year donate organs upon death, while more than 70,000 Americans are on waiting lists for transplants at any given time. Every year, according to the United Network for Organ Sharing, about 5,000 people die while waiting for a transplant. "There are clearly problems with the donor supply that will limit islet transplants from being a widespread therapy," says David Harlan, MD, head of the transplant and autoimmunity branch at the NIH. Some Possible Solutions Yet despite all those discouraging statistics, many researchers predict they will be able to get around the supply problem, likely during Ryan Dinkgrave's lifetime. One way is to grow islet cells in a laboratory and deliver them to surgeons for transplant. Scientists at several universities around the nation, including Harvard Medical School, are working on various methods of doing this. The Harvard researchers announced last month that they had successfully grown insulin-producing islet cells in the lab, but cautioned that theirs is just an initial step. They were able to grow 30,000 islets -- a fraction of the 700,000 needed for a successful transplant. And it may be years before the experimental cells can be tested in humans. Also, while growing them isn't difficult, getting such a complex grouping of cells to function in the body is. Researchers have been experimenting islet transplants for decades, but only now have such transplants become consistently successful. To get around this hurdle, Fred Levine, MD, a researcher at the University of California, San Diego, is trying to develop a line of beta cells, the cells that actually produce insulin. Beta cells grown in a lab must be highly genetically modified in order to reproduce, detect glucose levels, and produce insulin. Levine says he is confident beta cells can be engineered to produce enough insulin to cure diabetes, and he hopes to begin studies in humans in four or five years. But other researchers aren't so sure. Scientists must insert genes to make the cells grow in the lab, and it's conceivable those genes could get out of control and create cancerous cells. Also, past transplants of beta cells have failed, says Lakey. A third possibility is to mass-produce islet cells in the pancreases of pigs, which are similar to human pancreases. Supply is no problem; we can easily raise enough pigs. But this process raises its own difficulties. Though similar, the cells of pig pancreases still must be genetically modified to be compatible with human tissues. Those cells may prompt severe immune responses in people, which could cause rejection. Also, some scientists worry that pig viruses could adapt to humans and cause new diseases -- just as the human immunodeficiency virus (HIV) did when it jumped from monkeys to people, resulting in AIDS. So where does all this leave most diabetics and their families? For the moment, probably right where they were before this summer's breakthrough was announced: Waiting. Steady Progress and Hope Ryan Dinkgrave and his mother, Kathi, have followed scientific progress on diabetes closely for seven years, ever since he was diagnosed at age 10. They remember the initial excitement -- and disappointment -- over the islet cell transplants in past years. They recall feeling jubilant over other "revolutionary" advances like insulin eyedrops and infrared glucose monitors. And they remember the dashed hopes when these supposed breakthroughs failed to pan out. Still, they've seen steady progress. Kathi is convinced a widely available cure will come during her son's lifetime. But Ryan is keeping his optimism in check. If the islet transplants prove successful in the next round of trials, due to begin this fall, he hopes to put his name on what will undoubtedly be a long list of diabetics awaiting treatment. But even if the new trials are a success, young and relatively healthy patients like Ryan may not be allowed to undergo the procedure. Doctors remain unsure about the long-term effects of the immune-suppressing drugs that transplant patients need to keep from rejecting the islet cell transplants. Most likely, only high-risk, older patients will be candidates -- at least until more is known. Until then, Ryan will continue as he always has. He'll play his guitar and work at his summer job in a local bakery. He'll also prick his finger four times a day to test his glucose levels, check the insulin pump he wears on his body constantly, and eat on a tight schedule -- all in the name of keeping his blood sugar under control. For now, he can't quite bring himself to say the "C"-word. "I'll believe it when I actually do see it," he says. _________________________________________________________________ Get your FREE download of MSN Explorer at http://explorer.msn.com
