A transplant of genetically modified insulin-producing cells has controlled blood sugar levels in mice with type 1 diabetes, the most severe form of the disease, and has done so for the first time without the need for immunosuppressive drugs.
The advance, achieved by scientists from the University of California at San Francisco (UCSF) and the company Sana Biotechnology, opens the way for people with type 1 diabetes to live without the need to inject insulin. After the success of the treatment in mice, Sana Biotechnology plans to carry out clinical trials in people in the near future, the company has informed La Vanguardia.
Type 1 diabetes, which usually begins in childhood, is characterized by the destruction of insulin-producing cells in the pancreas. This forces those affected to inject insulin throughout their lives to regulate their blood sugar level, or glycemia. It also forces them to constantly monitor their blood glucose to avoid dangerous increases or decreases in sugar, which can cause -among other complications- cardiovascular, kidney, eye damage, coma and death.
Insulin-producing cell transplants have shown in recent years that they can restore adequate glycemic control in diabetics. But they force you to take immunosuppressive drugs to prevent these cells from being attacked by the patient’s immune system. Since immunosuppression has potentially more serious side effects than diabetes itself, this type of therapy has hitherto not been suitable for most patients.
Researchers at UCSF and Sana Biotechnology have solved this problem by creating what they call hypoimmune cells. These are insulin-producing cells that cannot be recognized or attacked by the immune system. Using the Crispr gene-editing technique, they have removed genes that make proteins that trigger immune reactions. Specifically, they have eliminated the class I and II MHC (major histocompatibility complex) genes.
In addition, they have boosted the gene for the CD47 protein, which functions as a stop signal for the immune system: when immune cells encounter CD47, they refrain from attacking. They have also done it as a precautionary measure: if the transplant of genetically modified cells had any unwanted effects, an antibody directed against CD47 could eliminate them.
The researchers have worked with iPS-type human stem cells, turned them into insulin-producing cells like those of the pancreas, and transplanted them into humanized diabetic mice, that is, a type of mouse that has type 1 diabetes like humans.
According to the results presented today in the journal Science Translational Medicine, the animals have correctly regulated their blood sugar level without the need for insulin injections. And they have done so without receiving immunosuppressive treatment, which indicates that their immune system has not attacked the transplanted cells.
“Our goal is to develop a stem cell-derived pancreatic cell therapy that can be administered without immunosuppression,†Sonja Schrepfer, director of Sana Biotechnology’s Hypoimmune Platform, who led the research, said by email.
The therapy will be delivered as an intramuscular injection, and not into the pancreas, the same strategy that has worked in mice. Muscle tissue has a good blood supply, which encourages insulin to reach the blood and allows the implant to be easily monitored with imaging techniques, the researchers report in Science Translational Medicine.
We will have to wait for the results of clinical trials to assess how long the efficacy of the transplanted cells lasts. In two previous studies of diabetic patients treated with immunosuppressants, and who have received insulin-producing cell transplants, efficacy has been maintained for an average of about five years. “There is data to suggest that many immunosuppressive drugs can be toxic to insulin-producing cells, giving us hope that our treatment could last even longer,†says Sonja Schrepfer.
Sana Biotechnology is currently collaborating in a clinical trial led by academic researchers who have developed a similar hypoimmune cell-based therapy for type 1 diabetes, reports the researcher. The company hopes to present the first data on the efficacy and safety of the therapy in patients later this year.
These data will guide the development of Sana Biotechnology’s treatment, which plans to apply for authorization as an experimental therapy in the United States next year.