Newswise — As the fourth-leading cause of death in developed countries, diabetes can truly be called a modern-day plague. While insulin injections help stabilize the condition, they do not provide a cure. Transplantation of insulin-producing islet cells from human donors or cadavers, an investigational approach to long-term diabetes treatment, is fraught with difficulties. San Diego-based MicroIslet, Inc. believes that transplantation of encapsulated islets from pigs may be the answer. The company has demonstrated proof of principal of this idea through multiple animal studies, and is set to begin human clinical trials of its revolutionary technology this year.
At the recently completed Global Diabetes Summit in Columbus, OH (Nov. 29-Dec. 1, 2007), MicroIslet's President and Chief Scientific Officer, Dr. Jonathan Lakey, explained the potential for treating diabetics with pig islet cells. "Xenotransplantation [from one species to another] has the potential to solve many of the problems associated with the transplantation of islet cells from one human to another," he said. Dr. Lakey presented compelling animal data from his company's preclinical studies and outlined the likely scenarios under which pig islets could one day emerge as a significant treatment modality for type 1 diabetes.
Diabetes has become a global epidemic with a huge economic impact. More than 194 million people worldwide have diabetes. About 10% of them have type 1 diabetes, which typically arises early in life and requires insulin injections several times a day. The International Diabetes Foundation estimates that diabetes care consumes 10% of the global healthcare budget " $132 billion in the U.S. alone. Most of that cost goes toward treating a dizzying array of serious, often life-threatening complications that include kidney failure, blindness, and poor circulation that can lead to a loss of limbs.
Despite advances, insulin therapy is clearly not the optimal answer to treating diabetes. A healthy pancreas produces insulin only when it is needed, and in just the right quantities, in response to subtle biological signals. Diabetics measuring insulin doses in a syringe can only approximate this complex mechanism. Accordingly, even with strict monitoring, many diabetics succumb to some of the diabetes complications listed earlier.
An experimental surgical technique known as islet cell transplantation has been successfully used to restore the body's insulin-producing capabilities. The operation involves harvesting insulin-producing islet cells from the pancreas of an organ donor and injecting them into the portal vein, or the interperitoneal cavity. Transplanted cells take up residence and, if all goes well, the cells begin to make insulin in response to ingestion of sugars and starches, similarly to how a normal pancreas operates.
Islet cell transplantation has met with limited success for several reasons. Because the body recognizes transplanted cells as "foreign" it tries to eliminate or "reject" them, which is seen in the transplantations of kidneys, livers, and other organs. Patients receiving islet cell transplants must therefore take anti-rejection drugs for the rest of their lives " or the life of the transplant. The tradeoff in reducing or eliminating insulin is the need to take immunosuppressive drugs. For this reason, islet cell transplants are currently only given to patients who cannot control diabetes or its complications through insulin injections, or who are already undergoing organ transplantation due to diabetic complications.
Another problem with islet transplants is the lack of availability of quality human pancreases. The donor organ shortage is compounded by the relatively low abundance of islets among pancreatic cells. Often two organs are needed to obtain sufficient cells to make the transplant work.
Even when transplanted islet cells take hold and produce insulin in the new host, the effect may not last very long. Possibly as a result of rejection, islet cells gradually lose their ability to produce insulin. In a study published in 2005, only 40% of recipients were off insulin a year after transplantation. After three years, the number fell to 17%. On the bright side, however, most patients were able to use less insulin, and appeared to manage their disease better.
MicroIslet's innovation involves the use of islet cells extracted from the pancreases of a very unique, and highly quarantined, herd of pigs. Normally such cells would be immunogenic since they are derived from another species. MicroIslet's technologies mitigate the problem of tissue rejection by encapsulating the islet cells in a biocompatible material known as alginate, a viscous gum derived from seaweed and used worldwide in many food, dental, and medical products. A protective covering of alginate allows the islet cells to receive nutrients and excrete insulin and waste products through the bloodstream, while also serving as a barrier that blocks the host's immune system from entering the capsule and thereby destroying the transplanted islets.
MicroIslet's approach holds numerous advantages over conventional islet cell transplantation. Because the islet cells are harvested from pigs, the supply is virtually unlimited and the reliance on organ donors is eliminated. Moreover, the process is tightly controlled from cell harvesting through the preparation of the transplantable cell formulation. Such care results in cells that are more robust and consistent than those obtained from cadavers.
Patients receiving pig islet cells will not require chronic immunosuppressive drugs, which will greatly improve their quality of life. Nor will the procedure involve any tradeoff between one burdensome drug regimen (insulin) and another (anti-rejection drugs). "Removing these barriers greatly expands the number of diabetics who might benefit from transplantation," Dr. Lakey noted.
MicroIslet has demonstrated proof of principal for its novel diabetes treatment in several animal studies. Transplanted porcine islet cells were successfully grafted into mice and monkeys, providing the animals with self-regulating glucose control. No adverse safety events were noted in test animals.
Armed with their animal data, the company has already presented their case for testing encapsulated pig islet cells in humans to the U.S. Food and Drug Administration. On December 7, 2007, the company had a pre-IND meeting with FDA, and expects human trials to begin in 2008. For more information, log on to http://www.microislet.com