I was fortunate to be able to attend the International Society for Stem Cell Research (ISSCR) Annual Meeting in June. Last week, I began a series of blogs related to information from the meeting and this series will continue over the next several weeks. Today’s blog will focus on an area that received quite a bit of coverage at the meeting cell therapies in development, in particular – Diabetes. At ISSCR there were several talks on Diabetes including a concurrent session dedicated entirely to the subject that primarily focused on aspects associated with the creation of pancreatic beta cells from human pluripotent stem cells.

In addition to the concurrent session, there was also an excellent plenary talk given by Dr. James Shapiro, University of Alberta, Canada titled Islet and Stem Cell Transplantation: Diabetes Therapies in the Clinic. In the presentation, Dr. Shapiro described both the historical progress of islet transplantation and some of the challenges. The diabetes coverage at ISSCR prompted me to write about the progress being made in the area of cell therapies for treatment of Diabetes.

What is Type 1 Diabetes Mellitus?

Type 1 diabetes mellitus, sometimes referred to as juvenile diabetes, results from immune-mediated destruction of insulin-producing islet cells in the pancreas and usually appears in childhood or adolescence.

Insulin is the standard treatment for Type I Diabetes, but the use of insulin can be challenging in some patients and achieving optimal glycemic control can be very difficult. Patients are required to regularly test their blood sugar levels and administer insulin accordingly. Blood glucose levels are changing regularly due to many factors can affect levels including diet, exercise, illness, stress, where you inject the insulin and when you inject it. As a result, some patients can find themselves in a state of hypoglycemia (low blood glucose levels) or hyperglycemia (high blood glucose levels). Severe hypoglycemia can cause seizures, coma and death. If left untreated, hyperglycemia can cause ketoacidosis or diabetic coma.

As a further complication, some patients have hypoglycemic unawareness, which is a condition in which they cannot feel the symptoms of hypoglycemia and as a result often don’t get treatment for themselves in time. Due to these challenges, other treatment options are often necessary for some patients. One of these options is a pancreas transplant, which provides better glycemic control for patients, however with it comes the risk of surgical complications and required immunosuppression.

Islet Transplantation

Islet transplantation is another treatment option. In islet transplantation, islets are harvested from the pancreas of an organ donor and cells are then infused into the liver. According to the National Diabetes Information Clearinghouse, “Transplant patients typically receive two infusions with an average of 400,000 to 500,000 islets per infusion. Once implanted, the beta cells in these islets begin to make and release insulin.”

Initial islet transplantation studies involved the transplantation of islets alone and this had a lower success rate, with most patients needing to return to insulin. However recent advancements have resulted in greater success. Dr. Shapiro discussed six study centers that reported 5-year insulin independence rates at over 50% when the islet transplant was combined with T-depletional inductional immunosuppression and anti-inflammatory antibodies.

One enabling technology for islet transplantation that was mentioned during Dr. Shapiro’s talk is a delivery system being developed by Sernova called a Cell Pouch System. The Cell Pouch System consists of a business card size medical device designed to hold cells. The Cell Pouch is implanted subcutaneously and allows cells to live and function within the body, while still being confined to one specific area. While there are many possible applications for this product, their first target is for the transplantation of islets. Utilizing this system allows islets to achieve long-term survival and function and to release insulin based on circulating glucose levels. In animal models glucose control was achieved using a combination of the Cell Pouch System and transplanted islet cells.

Sernova is currently recruiting participants for a Phase I/II clinical study to look at the safety and efficacy of the Cell Pouch System with islet transplantation for Type 1 Diabetes. The participants will receive the cell pouch implanted subcutaneously 2 to 12 weeks prior to the transplantation of islets into the cell pouch.

Currently in the U.S., islet transplantation is considered an experimental procedure, but that may change soon. Dr. Shapiro stated in his talk abstract “A large Phase 3 trial in North America, conducted under FDA jurisdiction, will likely lead to Biological Licensure for islet transplantation in the U.S. within the next 2 years.” While islet transplantation can provide a good therapeutic option, there are challenges to widespread adoption of this kind of therapy, primarily the availability of islet cells from donor organs.

Stem Cell Therapy

Since it has been demonstrated that islet transplantation can provide a possible therapeutic option, but a large supply of donor cells would be needed, it seems that expanding cells as a therapeutic would be a great candidate for clinical studies.

One company working to develop a stem Cell Therapy for treatment of Type 1 diabetes is Viacyte. Viacyte has developed a combination product called VC-01. The product attempts to mimic the functions of and provide a replacement endocrine pancreas. The product consists of two parts, first the PEC-01 cells, which are pancreatic endoderm cells derived through directed differentiation of embryonic stem cells. The second component of the product is their Encaptra drug delivery system; an encapsulation medical device that provides a semi-permeable cell containment barrier that protects the PEC-01 cells from immune cells. While keeping the immune cells out, the barrier does allow nutritional inputs to come in. These nutritional inputs primarily consist of glucose, O2 and proteins. These inputs give the cells information needed to respond with insulin, amylin, and glucagon that can pass back out to the body through the barrier.

The product is implanted under the skin where the cells can further differentiate into mature pancreatic cells. The idea is that after they become mature pancreatic cells, the cells will be able to receive nutritional inputs from the body and then respond by synthesizing and secreting therapeutic insulin and other factors. The hope is that the cells will ultimately function like a pancreas by regulating blood glucose levels through monitoring inputs and responding with the appropriate therapeutic outputs.

Animal models have demonstrated good safety and efficacy and now the company is ready to proceed into clinical trials in humans. According to a recent article in the San Diego Tribune, “Diabetes Stem Cell Therapy Readied,” Viacyte has applied to start a Phase I/II human clinical trial to assess safety and efficacy in Type 1 Diabetes. The company hopes that the first patients will be treated sometime in August or September.

Summary

It is exciting to see the extent of work being done around using cells to treat Type 1 Diabetes. It is possible, depending on clinical trial outcomes, that islet transplantation may be approved for treatment in the U.S. in the next couple years. While this is a good option now, the demand for donor cells may necessitate the development of a therapy using human pluripotent stem cells where cells could be expanded in culture and would thus eliminate the problem of high demand on donor cells. While the development of such a therapy, like the one Viacyte is taking to clinical trials, shows much promise, much work still needs to be done to make it a reality. These new developments offer a great deal of hope for those with Type 1 Diabetes that sometime in the future they will be able to get rid of the blood sugar monitoring kits and needles and rely on cells to replace the natural functions of the pancreas.

To learn more:

The journal article “Islet Transplantation at the University of Alberta: Status Update and Review of Progress over the Last Decade,” published in the Canadian Journal of Diabetes and on which Dr. Shapiro is an author is a great resource for additional information.

• www.clinicaltrials.gov
• www.viacyte.com
• www.sernova.com
• ISSCR Series

This is just the second in a series of blogs covering ISSCR 2014. It was an excellent meeting and I highly recommend attending if you get the opportunity. Find out more about the ISSCR’s 2015 Annual Meeting in Stockholm, June 24-27 by visiting – ISSCR’s 2015 Annual Meeting

ISSCR Series Blogs

• “Innovations Abound at the 2014 Annual International Society for Stem Cell Research (ISSCR) Meeting”