By Andrew Briskin – Link to Article
In a collaboration between ViaCyte and CRISPR Therapeutics, a new clinical trial is investigating a cell therapy that may eventually help millions with type 1 diabetes.
Researchers have long sought a cell-based “cure” for type 1 diabetes, and in recent years, this goal has seemed more attainable. Since the condition results from the body’s own immune system destroying the insulin-producing beta cells in the islets of the pancreas, research has focused on finding a way to replace these non-functional cells with new and functional beta cells.
There are now two main methods for generating new and functional beta cells. People can undergo a surgical procedure to transplant healthy insulin-making cells (called beta cells) from a human donor into a person with type 1. Alternatively, researchers have now discovered ways to generate beta cells from stem cells, or cells that have not yet matured into one of the many types of cells in the human body. In 2021, Vertex performed the first successful beta cell transplant in a person with type 1 with functioning beta cells created from stem cells. In that same year, ViaCyte published the first peer-reviewed studies showing that its own stem cell therapy was successful in producing insulin in people with type 1 diabetes.
The drawback to these procedures, however, is that they require recipients to take medicine to suppress their immune system on a daily basis in order to stop the immune system from attacking the implanted cells. While both methods could be considered functional cures for type 1 diabetes, the need for permanent immunosuppressants is a limitation.
However, a new cell therapy developed at ViaCyte, in collaboration with CRISPR Therapeutics, may answer the call.
CRISPR gene-editing technology, often referred to simply as “CRISPR,” is a Nobel Prize-winning technology that allows researchers to alter the genetic code (or DNA) of a cell with extreme precision. CRISPR is one of the most common methods used to create genetically modified organisms, agricultural products, and certain medications.
With current stem cell treatments (like the cell therapy used in Vertex’s current clinical trial), when a person with type 1 receives a beta cell transplant, the implanted cells have their own unique immune “signature” in their genetic code, which is different from that of the recipient. This is why the body’s immune system thinks of the cells as foreign and dangerous, so it will target them for destruction in the same way that a person’s own beta cells are targeted for destruction when they have type 1.
By altering the genetic code of these implanted cells using the CRISPR technology, however, researchers may be able to create beta cells that avoid all recognition by the immune system, creating cells that might evade the attack from the immune system completely.
“This new product could provide a functional cure for type 1 diabetes,” said Dr. Howard Foyt, chief medical officer at ViaCyte. “By implanting these cells in the individual, the hope is that people can throw away their glucometers and insulin syringes, because these cells could provide all the insulin they need.”
According to ViaCyte, pre-clinical studies (which are done in test tubes or in animals, prior to being tested in humans) showed that these beta cell implants were well-tolerated, and had minimal side effects.
This therapy (called PEC-QT) places genetically modified beta cells (that will hopefully be invisible to the recipient’s immune system) into a pouch that is then implanted into the body. Blood vessels should be able to grow and penetrate the pouch coming into direct contact with the cells and giving them all the nutrients and oxygen they need.
“The advantage of having these cells in the pouch is that we can remove them all at once, unlike a typical islet cell transplant or cell infusion,” Foyt said. “So being designed for safety is a big advantage with this procedure. If someone does have an immune reaction, we can remove the cells.”
There are still several questions that need to be answered about these therapies, one of which is how often the pouch needs to be replaced.
“We refer to this as a potential ‘functional’ cure for type 1 diabetes because the device is not permanent; we know it will need to be replaced after a certain time,” Foyt said. “To an extent, because cells directly contact the blood, the pouch is akin to islet cell transplantation. If so, we could potentially see a lifespan of potentially five years, similar to islet transplants, and possibly as long as 10 years, but this question remains unanswered.”
Another therapy (called PEC-Encap), now in Phase 2 clinical trials, places the modified beta cells into a pouch that blood vessels and immune cells cannot penetrate (a method called encapsulation), but that allows nutrients such as oxygen, glucose and other hormones to pass through the walls of the pouch.
While it will be several years before PEC-QT and other beta cell therapies hopefully become available for people with type 1 diabetes, the beginning of these clinical trials is another step toward the goal of finding a cure for type 1 diabetes.
On Feb. 2, ViaCyte and CRISPR Therapeutics announced that the first participant in the trial had received the PEC-QT implant. This marks the first gene-edited, stem cell-derived pancreatic cells to be implanted in a human that are specifically designed to evade the immune system in treating type 1 diabetes.
All in all, Foyt is optimistic that this therapy could eventually be used by a large portion of the type 1 population, if not people with insulin-requiring type 2 diabetes as well.
“This is the power of stem cells,” he said. “We have the capacity to create a seemingly unlimited supply of gene-edited stem cells to be used in developing this functional cure for type 1 diabetes.”
For more about the latest in the search for type 1 cures, stem cell therapy, or efforts to tackle immunosuppression, check out these articles:
