Ron Evans steals I / O stuff and leads the way in transformational diabetes therapy – Endpoints News

Salk Institute scientist and serial biotechnology entrepreneur Ron Evans yesterday showed new work in mice that could point to a long-sought holy grail for the treatment of diabetes.

The study, published in Nature, involved a new approach for islet cell transplantation, a therapy for diabetes where dysfunctional insulin-producing cells on the pancreas are replaced by functional cells. The treatment has been around for some time and new ones are in development, but they have been hampered by the fact that patients will reject cells unless they take immunosuppressive drugs.

But, working with iPSC stem cells and immunotherapy tricks, Evans and his team developed what they called “immuno-evasive” groups of cells – essentially mini pancreas. Placed in mice, these cells secrete appropriate amounts of insulin without being under fire from immune cells, paving the way for a similar approach in humans.

“Most type 1 diabetics are children and adolescents,” Evans said in a statement. “We hope that regenerative medicine, combined with an immune shield, can make a real difference in the field by replacing damaged cells with clumps of human islet-like cells generated in the lab that produce normal amounts of insulin at home. request.”

Evans, who recently co-founded and sold the biotechnology “exercise pill” Mitobridge to Astellas, and his co-authors are hardly alone in this race. ViaCyte has received major support from private donors and the Juvenile Diabetes Research Foundation for their own stem cell-derived islet cell transplant. Flagship also launched Sigilon earlier this year with $ 80.3 million in Series B funding. With technology from Robert Langer, the company is developing polymers that can encapsulate cells for transplantation. A program to fight diabetes is activating the IND with Eli Lilly.

Four years ago, Evans and his team discovered how to make functional pancreatic beta cells for the first time, using a series of molecular switches to cause them not only to produce insulin, but also in response to glucose, as do normal cells. But that still left questions about how to switch from single cells to pancreatic-like clusters and how to get those cells to bypass the immune system during transplantation.

To group cells together, Evans’ lab found that a protein involved in embryonic development called WNT4 could trigger the same molecular mechanisms that created functional beta cells. The addition of this protein led to the creation of 3-D clusters of cells similar to what we would see in humans. They called them human islet-like organoids, or HILO.

Evans, with Downes and Yoshihara

To make these organoids, Evans and Eiji Yoshihara, a scientist in his lab, stole something from another field: immuno-oncology. Using short pulses of a protein called gamma interferon, Yoshihara allowed cells to express PD-L1.

PD-L1 had the opposite effect of PD-L1 inhibitors used in cancer. Rather than making sure the T cells saw a tumor, they made sure that the T cells did not see the islet cells.

“This is the first study to show that you can protect the immune system’s HILOs without genetic manipulation,” said Michael Downes, an author of the journal. “If we are able to develop this as a therapy, patients will not need to take immunosuppressive drugs.”