Some diabetics have found success in an experimental treatment that injects insulin-producing cells into the body, writes JAMIE TALAN
SINCE age 13, Ellen Berty has had to worry about having food in her pocket – just in case she was stuck somewhere and her blood sugar levels were precariously off-balance. Diagnosed with Type 1 diabetes, Berty, 54, defied the odds of serious complications from diabetes until about three years ago. Without warning, she would fall into unconsciousness, her body suffering a severe hypoglycemic reaction.
But the preschool educator from Arlington, Virginia, no longer worries about blackouts or emergency food supplies or, for that matter, the multiple daily injections of insulin that kept her alive for the past 40 years. She is one of a fraction of diabetic patients in the United States who have received an experimental islet cell transplant that – at least for now – has stopped her illness.
“Am I still a diabetic?” Berty asks. “Well, I haven’t needed insulin for 20 months, and my average blood sugar is normal. It’s been fantastic. I’d do it again in a flash.”
With islet cell transplants, scientists inject hundreds of thousands of the cells (culled from the pancreas of a donor cadaver) through a vein into the liver. The cells then produce insulin, which carries out its job of regulating blood glucose.
Since 1999, when Canadian researchers announced the first consistent success with the cell transplant, diabetics in the United States have put their names on waiting lists for the still experimental procedure.
For a variety of reasons, they may never get their wish. So far, fewer than 60 US patients have gained entry into the handful of clinical trials.
Even if it becomes a federally approved procedure, meaning that patients can be reimbursed for the transplant and lifetime supplies of anti-rejection medicines to keep the cells alive, there are simply not enough organ donors to cull enough pancreatic islet cells to treat even 1% of the 1.5 million Americans with Type 1 diabetes, scientists say.
“There are still a lot of hurdles to overcome before this therapy is ready for widespread application,” said Dr David Harlan, chief of the transplantation and autoimmunity branch at the US National Institute of Diabetes and Digestive and Kidney Diseases. “For now, we caution patience. Good research is just painfully slow.”
The success rate for the patients who received islet cells from doctors at the University of Alberta in Edmonton is about 85% one year after transplant, and the US studies are showing similar benefits. Some of these patients still require insulin, but smaller amounts.
For others, the risks of the procedure and the anti-rejection medicines have outweighed the benefits. There have been infections, internal bleeding, side effects from the anti-rejection medicines and rejection of the cells themselves. Right now, it isn’t possible to tell whether a patient will benefit from the transplant, doctors say.
But when it works, it is akin to a miracle. That’s the way Gary Kleiman sees it. Kleiman has been a Type 1 diabetic since he was seven. The 50-year-old executive director of medical development at the Diabetes Research Institute, part of the University of Miami, underwent an islet transplant late last year.
He has not had to inject himself with insulin since.
“It’s been breakthrough work,” Dr Andrew Drexler, director of the New York Diabetes Programme and a clinical associate professor at NYU School of Medicine in Manhattan, said of the Edmonton study. “Now, it’s been confirmed by others, but we need to find a way to have it work for a larger number of patients. We are nowhere near that point.”
The guidelines of entry into these restricted studies mean few patients qualify. Only adults with Type 1 diabetes who have severe swings in blood glucose levels that can’t be controlled with insulin injections can apply. Overweight patients also are ineligible, because even thin patients need islet cells from two independent donors, and that cuts into the already short supply of human donors. (Scientists estimate that there were about 6,000 pancreatic organ donations last year, and only 1,500 were viable enough for transplantation, according to University of Miami’s Dr Camillo Ricordi, director of the Diabetes Research Institute.)
While there are serious research obstacles to overcome, it ultimately may be another organ supply-demand issue. Drexler said that the pancreas often falls last on the organ donor chain, with attention paid to removing the liver and kidney first, often damaging the pancreas in the process. And the islet cells make up only 5% of the pancreas, making it even less likely that healthy cells can be salvaged.
Dr Fouad Kandeel of the City of Hope National Medical Centre said that his California hospital is one of 10 recently selected by the US federal government to isolate and distribute islet cells for clinical trials. They will procure pancreases carefully and develop ways to keep the cells alive and healthy long enough to transplant. The Edmonton protocol, used in many US trials, calls for their use within two hours.
But scientists are developing ways to extend the lives of these donor cells. Ricordi and his colleagues have devised a method to keep islet cells alive for up to three days in culture. The islet cells have already been shipped to Baylor College of Medicine in Houston, where seven patients have received transplants.
Ricordi has received approval from the Food and Drug Administration to begin human studies of a technique developed at his hospital that could bypass the need for anti-rejection medicines. The concept, donor-specific immune tolerance, is to fool the body into thinking the donor cells are not foreign. It’s the immune system’s job to fend off foreign cells.
The experimental technique calls for removing bone marrow stem cells as well as the pancreas from the same donor. The idea is to inject the bone marrow into the patient’s blood while sending the donor islet cells into the liver. In a short time, the body’s new immune cells would recognise the body’s new islet cells as relative, not foreign. It’s worked in animals and human patients are now lining up. Ricordi has federal approval for transplant in 12 patients.
No one knows yet what the long- term effects of the transplants will be. – LAT-WP
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