Another Progress Report on Islet Transplantation

In my 2007 Wrap-Up and Outlook for 2008, I had noted some progress made towards curing type 1 diabetes. Specifically, I noted the work being undertaken by New Zealand-based Living Cell Technologies, Ltd. (LCT), as that company is now undertaking human clinical trials in Russia. I hadn't mentioned another company, this one based in San Diego, California named MicroIslet, Inc., a biotechnology company engaged in the development and commercialization of transplantation therapies for diabetes. I chose not to report on MicroIslet's innovations not because of lack of progress, but because MicroIslet is not as far along in trials of their product as LCT is with theirs. Perhaps did a disservice in not reporting it, therefore, I am reporting on their 2007 progress today.

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.

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.

Then, in December 2007, MicroIslet also announced that it had met with the U.S. Food and Drug Administration (FDA) to discuss requirements for the filing of an Investigational New Drug (IND) application for MicroIslet-P™, a microencapsulated suspension of pancreatic islet cells.

As a result of the FDA meeting, MicroIslet has clarified details of the development path for its xenotransplantation approach, which involves microencapsulation of insulin producing porcine islet cells. The Company's last meeting with the FDA in December 2006 related to a proposed IND for allotransplantation of microencapsulated human islet cells. [this means the islets are encapsulated in the company's proprietary casing which enables insulin to be released without The Company's current strategy is to proceed directly to human clinical trials of its xenotransplantation approach, which overcomes the inherently limited supply of human islets. The proprietary encapsulation methods used in MicroIslet-P™ are designed to shield the islet cells from immune system rejection, while the planned implantation procedures will be minimally invasive. The Company's pre-clinical testing to date has demonstrated a strong safety profile for xenotransplantation of porcine islets in rodents and non-human primates.

The company notes that 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 also 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 really 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. Furthermore, there is also evidence that the incidence of severe hypoglycemia, a side-effect of treatment with insulin, is significantly reduced as a result.


Will MicroIslet's or LCT's innovations enable more patients to receive islet transplants with a higher degree of success than those who received the original "Edmonton Protocol" did? Perhaps, but clearly, it's a race between them and rival LCT to see who gets there first ... successfully. Only time will tell, but clearly, any improvement upon the the success of islet transplants is an advance. However, I would caution that there is also growing evidence that the chosen location of the transplant, so far being done in the liver, may also contribute to the less-than-successful long-term results. After all, if nature had intended islets to be in the liver, wouldn't they be there in the first place? We can expect more progress made by both companies in the coming year. No doubt, 2008 will bring more advances in this field of islet transplantation which cannot be overlooked!