Stem Cell Agency Board Approves New Clinical Trial for Type 1 Diabetes

Dr. Peter Stock at the capitol in Sacramento in May 2016.
Photo courtesy of Steve German.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $11.08 Million to Dr. Peter Stock at the University of California San Francisco (UCSF) to conduct a clinical trial for treatment of Type 1 Diabetes (T1D).

The award brings the total number of CIRM funded clinical trials to 54. 

T1D is a chronic autoimmune disease that affects approximately 1.25 million Americans, with 40,000 new diagnoses each year.  T1D occurs as a result of the body’s immune system destroying its own pancreatic beta cells.  These cells are necessary to produce the vital hormone insulin, which regulates blood sugar levels in the body.  As a result of a lack of insulin, there is no blood sugar control in T1D patients, gradually causing disabling and life-threatening complications such as heart disease, nerve damage, and vision problems.

There is no cure for T1D.  Current treatments consist of blood sugar monitoring and multiple daily injections of insulin.  Transplantation of beta cells, contained in donor pancreatic islets, can reverse the symptoms of diabetes.  However, due to a poor islet survival rate, transplants require islets from multiple donors.  Furthermore, since islet cells are transplanted directly into the vessels that enter the liver, it is extremely difficult to monitor and retrieve these cells should the need arise. 

Dr. Stock’s clinical trial at UCSF aims to address these limitations.  The trial will be using parathyroid glands to aid in the success and viability of the transplant procedure.  Co-transplantation of islets and parathyroid glands, from the same donor, substantially increases beta cell survival, potentially enabling adequate long-term insulin production and removing the need for multiple donors.  Additionally, the co-transplantation will occur in the patient’s forearm, which allows for easier monitoring and improves the effectiveness and accessibility of islet transplants for patients.

“This team’s innovative approach to develop a definitive cell-based treatment for Type 1 Diabetes has the potential to address an unmet medical need that exists despite advancements in diabetes therapy.” says Maria T. Millan, M.D., the President and CEO of CIRM.  “The success of this clinical trial could enable the successful application of islet cell transplants but also of future stem-cell based approaches for diabetes.”

CIRM has funded three other clinical trials for T1D.  One of these was conducted by Caladrius Biosciences and two by ViaCyte, Inc.

Breakthrough for type 1 diabetes: scientist discovers how to grow insulin-producing cells

Matthias Hebrok, PhD, senior author of new study that transformed human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

More often than not, people don’t really think about their blood sugar levels before sitting down to enjoy a delicious meal, partake in a tasty dessert, or go out for a bicycle ride. But for type 1 diabetes (T1D) patients, every minute and every action revolves around the readout from a glucose meter, a device used to measure blood sugar levels.

Normally, the pancreas contains beta cells that produce insulin in order to maintain blood sugar levels in the normal range. Unfortunately, those with T1D have an immune system that destroys their own beta cells, thereby decreasing or preventing the production of insulin and in turn the regulation of blood sugar levels. Chronic spikes in blood sugar levels can lead to blindness, nerve damage, kidney failure, heart disease, stroke, and even death.

Those with T1D manage their condition by injecting themselves with insulin anywhere from two to four times a day. A light workout, slight change in diet, or even an exciting event can have a serious impact that requires a glucose meter check and an insulin injection.

There are clinical trials involving transplants of pancreatic “islets”, clusters of cells containing healthy beta cells, but these rely on pancreases from deceased donors and taking immune suppressing drugs for life.

But what if there was a way to produce healthy beta cells in a lab without the need of a transplant?

Dr. Matthias Hebrok, director of the UCSF diabetes center, and Dr. Gopika Nair, postdoctoral fellow, have discovered how to transform human stem cells into healthy, insulin producing beta cells.

In a news release written by Dr. Nicholas Weiler of UCSF, Dr. Hebrok is quoted as saying “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”

For the longest time, scientists could only produce cells at an immature stage that were unable to respond to blood sugar levels and secrete insulin properly. Dr. Hebrok and Dr. Nair discovered that mimicking the “islet” formation of cells in the pancreas helped the cells mature. These cells were then transplanted into mice and found that they were fully functional, producing insulin and responding to changes blood sugar levels.

Dr. Hebrok’s team is already in collaboration with various colleagues to make these cells transplantable into patients.

Gopika Nair, PhD, postdoctoral fellow that led the study for transforming human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

Dr. Nair in the article is also quoted as saying “Current therapeutics like insulin injections only treat the symptoms of the disease. Our work points to several exciting avenues to finally finding a cure.”

“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.” 

Dr. Hebrok, who is also a member of the CIRM funded UCSF Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, was senior author of the new study, which was published February 1, 2019 in Nature Cell Biology.

CIRM has funded three separate human clinical trials for T1D that total approximately $37.8 million in awards. Two of these trials are being conducted by ViaCyte, Inc. and the third trial is being conducted by Caladrius Biosciences.