Cell transplants at U of M could provide diabetes cure
Star Tribune (Minneapolis, MN)
MINNEAPOLIS _ Dave Thoen feared being alone at night, knowing he could be blindsided at any time by a debilitating, even deadly, seizure.
The Bloomington, Minn., actuary suffered from both diabetes and a condition called "hypoglycemic unawareness," which blocks the telltale signs of low blood sugar. Despite frequent blood tests and obsessive attention to diet and exercise, seizures could strike him like a hammer _ like the blackout that occurred one night during a business trip to Los Angeles. When Thoen regained consciousness, he found himself locked outside his room and covered in blood. His spasms apparently had caused him to bang his head repeatedly into the nightstand.
"I literally had to crawl to the hotel desk," Thoen recalled.
Today those fears are a memory. Thoen is one of 48 people to receive a set of groundbreaking experimental treatments at the University of Minnesota, which proved that transplants of insulin-producing cells known as "islet cells" can treat _ and sometimes cure _ Type 1 diabetes, one of the nation's most serious health scourges.
After more than three decades of research, a consortium of schools that includes the University of Minnesota has completed testing on the transplant technique. Now, the U is preparing to apply to the U.S. Food and Drug Administration for a license to become a manufacturing facility. University officials say a "biological drug license" would allow them to commercialize the new treatment, which has cost the U at least $25 million in grants and donations so far. That, they say, would represent a unique example of a university bringing a new treatment directly from academic research to human applications without any company funding.
"That is completely and entirely unheard of," said Dr. Bernhard J. Hering, who directs the project at the U.
If the FDA approves, Hering said, a doctor will be able to prescribe human islets instead of insulin injections. Somewhere between 60 and 70 percent of patients who receive the cells could expect to remain insulin-free after five years, Hering said.
Even those who must still take some insulin, like Thoen, say the operation is life-changing. Before the treatment, Thoen said, he felt guilty relying on family and friends to take care of him. After the treatment, he was able to take his two boys to the Boundary Waters Canoe Area Wilderness on a camping trip, something he says he wouldn't have dared in the past.
"The transformation for me has been just absolutely amazing," he said.
Some 26 million Americans have diabetes, and the number is growing at a pace that the U.S. Centers for Disease Control and Prevention has called "unsustainable."About 95 percent have Type 2 diabetes, which is often caused by poor diet and insufficient exercise. It occurs when islet cells in the pancreas fail to produce enough insulin _ a hormone that converts food into glucose _ or when the cells cease to recognize it.
About 1.5 million people have Type 1 diabetes, which results when the body's autoimmune system destroys its own islet cells. Of those, 100,000 share Thoen's condition of hypoglycemic unawareness.
People with unregulated diabetes face serious complications including blindness, heart and kidney failure, sexual dysfunction, nerve damage and death.
Stephanie Arneson, 49, of Rogers, Minn., was diagnosed with Type 1 diabetes at age 3. She tried everything to regulate her blood sugar, including an insulin pump, changes in her injection regimen and special training programs.
"Nothing seemed to help," Arneson said. "I would have the ambulance at my house three times a month."
The disease led to blindness in her left eye.
The last straw came when Arneson blacked out while driving and hit a concrete wall. Her doctor referred her to the experimental transplant program at the U. She rejected her first donor cells in 2001. But two additional transplants in 2003 took, and she's been insulin-free since.
Arneson, a human relations worker and mother of two daughters, said she never knew life without diabetes until then. In the past, for example, feelings of thirst indicated high blood sugar. She called Dr. Hering in a panic one time thinking that she must be rejecting her islet cells because she was thirsty, but her blood tests were normal.
"He said, 'Stephanie, people get thirsty,' " Arneson recalled. "This whole normal thing is so hard to get used to."
(EDITORS: STORY CAN END HERE)
The genesis of the U's islet transplant program came in 1974, when surgeons David Sutherland and John Najarian performed the first transplant from a deceased donor to a living recipient. Decades of research followed. The University of Alberta in Edmonton achieved a major breakthrough with a protocol using multiple donors, but the recipients returned to insulin after a year or two. In 2005, the U developed a new protocol to harvest cells from a single donor and reported last year that the recipients had remained off insulin, or nearly free of it, after many years.
"So now that has become the new standard," Hering said.
The procedure goes like this: When a donor pancreas becomes available, its islet cells are harvested and cleaned. Then they're injected through a small incision in the recipient's belly into a "portal" vein, which delivers them to the liver (the pancreas itself is fragile and hard to reach). They settle in and begin producing insulin. The patient then receives immunosuppressants, which keep the body from attacking the foreign cells.
(EDITORS: BEGIN OPTIONAL TRIM)
Lorna Zaworski, 47, of Minneapolis, was diagnosed with diabetes at age 9. She got a transplant of islets cells at the U in August 2000 and hasn't needed insulin in nearly 13 years. Asked to describe her life before the operation, she turned to her husband, Tom.
"I met her on the floor of the Northtown Mall," he said. "She was one of my better customers when I was working security there."
Tom Zaworski said Lorna had such brittle diabetes that he debated whether to marry her for five years. "She was starting to have lows behind the wheel. We nicknamed her 'Crash' because she crashed so many vehicles," he recalled.
Just a month after they finally married, she was put on the transplant list at the U, and six weeks later she received her islet cells from a donor in Oregon.
Unlike some patients, Lorna Zaworski hasn't suffered ill effects from the immunosuppressants, which can cause mouth sores, stomach problems, diarrhea, anemia and increased susceptibility to disease.
(END OPTIONAL TRIM)
For now, islet cells must be harvested from the organs of deceased donors. But with only 7,000 pancreas donors a year, and only 2,000 to 4,000 suitable for transplant, there won't be enough to go around. The U is at the forefront of research that could lead to a ready supply of islet cells, however, either from specially bred pigs that live in sterile pens, or from human stem cells.
Hering said he's betting on pigs, although the idea takes some people aback. They're easier to control for quality and consistency, he said.
Both technologies promise to eliminate the need for immunosuppressant pills and their side effects; some of the islet cells have been engineered to make insulin and other hormones, but also immunosuppressive medications.
"We have genetically engineered pigs with very unique islets," Hering said. "That is a reality. That's not just science fiction."
(c)2013 Star Tribune (Minneapolis)
Visit the Star Tribune (Minneapolis) at www.startribune.com
Distributed by MCT Information Services
PHOTOS (from MCT Photo Service, 202-383-6099): MED-DIABETES-CURE
GRAPHIC (from MCT Graphics, 202-383-6064): Diabetes cure
KeyWords:: BC-MED-DIABETES-CURE:MS BC MED DIABETES CURE MS