In search of a cure for diabetes

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When Donna Marcelissen opens her eyes in the morning, her world is no longer a soft-focus blur, like a Monet painting. She can make out faces where once there were only foggy silhouettes. She can see dimensions: plates no longer look as if they’re embedded in the table; she doesn’t always trip and stumble stepping off the sidewalk. And she is eating foods she never dreamed she would one day eat again, like bread and bagels – things that “were once taboo for me, worse than sitting and eating a chocolate bar. But now I can eat bread,” the Ottawa woman says as she looks into the camera. “It’s a gift.”

Ms. Marcelissen was the 33rd patient in Canada to undergo a revolutionary islet cell transplant at Edmonton’s University Hospital.

At a session on diabetes research at the Stem Cell Network’s annual general meeting, Dr. James Shapiro, the University of Alberta surgeon behind what is now known the world over as the Edmonton Protocol, described how the ground-breaking “drive-thru” transplant has rapidly moved from experimental research to the standard of care for Type 1 diabetes in the province in which it was pioneered – and how stem cells may one day turn the transplant into a life-giving treatment for hundreds of millions of people with diabetes worldwide.

So far, 38 patients in Canada have undergone the procedure, which involves transplanting insulin-producing islet cells removed from the pancreas of cadavers into the livers of patients with diabetes.

Eighty-two per cent of patients transplanted so far remain “insulin free”, or off their daily insulin injections, for at least one year, “with excellent glucose control,” says Dr. Shapiro, Director and Head of the Clinical Islet Transplant Program at the University of Alberta. Of those patients who have had their transplanted islets for three years, 89 per cent continue to have graft function, meaning they remain off insulin completely, or require far less insulin than they did before the transplant.

The procedure itself is “incredibly simple,” Dr. Shapiro says. A long, thin needle is inserted into the patient’s right side and into the main portal vein leading to the liver. Hundreds of thousands of islet cells are then pushed through the catheter. Once inside the liver, the cells take root and produce enough insulin to achieve almost perfect control of blood sugar. “This doesn’t require surgery. It’s carried out with ultrasound fluoroscopy. It takes about 15 to 50 minutes to gain access. Patients are in and out of hospital within 24 hours,” Dr. Shapiro said.

In a video produced by the transplant team at Edmonton’s University Hospital, patients described how they were able to remain awake for the entire procedure. “I felt really at peace and really at ease,” said one woman. “Literally the next day I walked out of the hospital.”

“The last time I took insulin was on August 26, 1999,” said another patient. “I’ve been more than three years without one single injection of insulin.”

Of 152 patients transplanted in more than 15 centers worldwide, “there have been no deaths, no cancers, no lymphomas,” Dr. Shapiro reports. But there is still a long way to go: The procedure is not yet ready for children, because of the possibility of acute or chronic rejection, the risk of infection and the side effects associated with the anti-rejection drugs, such as ulcers and hypertension. Researchers are working hard to improve safety and toxicity, so that patients would not have to remain on lifelong immune-suppression therapy.

But the single greatest hurdle is supply: It usually takes two donor pancreases to provide enough islet cells for a single transplant, but donor organs are in such scarce supply there are only enough islets from pancreatic donors to treat 0.1 per cent of patients who could benefit, Dr. Shapiro says. “Clearly we have to find a new source of cells if this is going to be practical therapy for people with diabetes.”

Stem cells could be the answer. The hope is that researchers will one day be able to use stem cells to generate a limitless supply of insulin-making beta and islet cells in the laboratory for transplant.

The national Stem Cell Network’s Diabetes Working Group is looking at different stem cell populations. Dr. Lawrence Rosenberg, of McGill University, for example, and his lab are focusing on adult human stem cells in pancreatic tissue and using a protein to turn those cells into insulin-making beta cells. Dr. Greg Korbutt, of the world-renowned University of Alberta islet transplant team, is looking at ways to turn stem cells from pancreatic ductal cells into functional islets.

The success of the islet transplant program is “just a tiny start” towards an eventual cure for diabetes, Dr. Shapiro says. “But it’s a spark of hope for every patient with diabetes.

“There’s been dramatic progress with embryonic and adult stem cell lines. Which is going to get there fastest? To my mind, it doesn’t matter, as long and it is safe and a more or less limitless supply. What’s important is that energetic, bright researchers are working in each of these fields.”

More than two million Canadians have diabetes, the leading cause of kidney failure, blindness and amputations. Diabetes and its complications kill more people than AIDS, breast cancer and lupus combined.

“The mission of the Juvenile Diabetes Research Foundation is to find a cure for Type 1 diabetes and we’re very excited about the potential of stem cell research for reaching that end,” adds Ann Caroll, associate director of research at JDRF, which is based in New York City. “JDRF has a history of investing in Canada and we are enthusiastic in supporting the Network. The talent and skill for islet transplantation combined with basic stem cell research together look promising as we go down the road towards a cure for diabetes.”

Donna Marcelissen remained insulin-free for three months after her transplant last April, “the best three months of my life.” She has had to return to a small amount of insulin, though only about one-sixth what she used to have to inject.

“I am on the transplant list for a ‘top up’,” she says. “We are hoping it comes very soon.”