In type 1 diabetes the immune system attacks and destroys insulin-producing islet cells in the pancreas. San Diego, Calif.,–based biotech firm MicroIslet Inc., is developing an islet therapy in which insulin-producing porcine islets are implanted in a person's peritoneum (the thin membrane lining the abdominal cavity) from an external catheter bag via a tube inserted into the stomach.
"Human-to-human islet transplants can work but there's not a commercial opportunity there because of limited access to pancreases [someone has to die]," says Keith Hoffman, a MicroIslet board member. This scarcity means "millions of people" do not have access to islet transplants that could bring their diabetes under control, he adds.
In MicroIslet's cell encapsulation method (developed at Duke University), the porcine islet cells are isolated from the human immune system using an alginate shell (a thickening agent derived from seaweed) so they can produce insulin when needed without being destroyed by human antibodies. Nutrients such as insulin, glucose and oxygen are able to diffuse freely through the alginate.
MicroIslet is not the only company searching for a diabetes treatment via encapsulated xenotransplantation (cross-species transplant). Australian biotech firm Living Cell Technologies, Ltd., is testing its DiabeCell neonatal porcine islets encapsulated in an alginate gel that can likewise be transplanted for the treatment of insulin-dependent diabetes. The first DiabeCell patient was implanted last June, and the company this year plans to complete a clinical trial in Russia. MicroIslet seeks to take this budding procedure further by improving the durability of microencapsulated islets so they resist rapid deterioration over time (although allowing the islets to remain fully responsive), thereby lengthening the time between implantations.
MicroIslet cautions that, while it believes xenotransplantation can be a therapeutic solution for millions of diabetics worldwide, it will not likely replace insulin injections for all diabetes sufferers. The transplant procedure may not be suitable for some diabetics and others may still have to take insulin injections (although not as frequently).
In 2005, the U.S. Centers for Disease Control and Prevention estimated that about 7 percent of the American population (20.8 million people) had diabetes (types 1 and 2)—and 6.2 million of them were unaware of it. About 21 percent of the U.S. diabetes patients are 60 years of age or older. The World Health Organization estimates that more than 171 million people have diabetes worldwide.
MicroIslet has tested their procedure on normal rodents and those with defective immune systems and is currently studying potential toxicity side effects. "Initial rodent studies were designed to look at the efficacy and duration of the implants," says Amaresh Basu, MicroIslet's vice president of research and development. Primate porcine-islet xenotransplantation trials are also underway.
While the prospect of porcine islet transplants holds much promise and "is one of the best options for (type 1 diabetes) treatment," the biggest obstacle will come from the human immune system's willingness to accept the new cells, says Ewan McNay, an assistant professor of internal medicine specializing in endocrinology at Yale University's School of Medicine in New Haven, Conn. "This is the case with any transplant surgery," adds McNay, who studies the effects of transplantation more generally. "Type 1 diabetes is an autoimmune disease to begin with, so it's likely those stem cells will face the same problems that the original pancreas had."
MicroIslet is hoping to begin human xenotransplantation trials by the end of the year. Candidates for the procedure will be diabetes patients who have received kidney transplants. "These are people who are encountering the same problems that attacked their original kidney," Hoffman says.
Pig insulin is a good candidate for xenotransplantation to humans because it differs from human insulin by only a single amino acid. Although the Food and Drug Administration has approved porcine organ xenotransplants, it is still unclear how long these new islets can remain functional in a human body, Hoffman says. "If they lasted six months to a year,'' he says, "you could have treatment at those intervals."
