Gene Editing and the Future of Pancreas Transplants: A Fresh Hope for Type 1 Diabetes
Four weeks after transplanting genetically modified insulin-producing cells into a patient with type 1 diabetes, researchers at Uppsala University Hospital achieved a breakthrough: the transplanted cells were alive and functioning, despite the patient not taking any immune-system-suppressive drugs. This marks the first time gene-edited cells have successfully evaded both transplant rejection and the autoimmune attack that defines type 1 diabetes (T1D).
The Burden of Type 1 Diabetes
Type 1 diabetes affects approximately 9 million people worldwide, according to the World Health Organization. Managing T1D requires meticulous attention to diet and insulin administration, impacting quality of life and reducing life expectancy by up to 10 years. Every carbohydrate intake must be carefully calculated, and insulin doses adjusted accordingly. Even with modern technology like continuous glucose monitors and insulin pumps, the disease remains a constant challenge.
Islet Transplantation: A Current Solution with Limitations
The Edmonton protocol, developed by James Shapiro and his team in Canada, revolutionized treatment by transplanting cadaveric donor islets into a person’s liver. This approach can allow patients to live without insulin therapy for years, but requires lifelong immunosuppressant medication. Supply of donor cells is limited, and the need for ongoing immunosuppression presents significant drawbacks.
“There just aren’t that many people for whom lifelong immunosuppression is better than lifelong insulin.”
The Promise of Hypoimmune Cells
Researchers are now focusing on creating “hypoimmune” cells – genetically engineered cells that evade immune detection. Sonja Schrepfer, a scientist at Cedars-Sinai, identified three key genetic modifications: knocking out HLA class I and class II molecules (major transplantation antigens), and overexpressing CD47, a “don’t eat me” protein. These modifications prevent both allogeneic rejection and autoimmune attack.
Sana Biotechnology’s Approach: Gene Editing for a Cure
Sana Biotechnology is pioneering this approach, using gene editing to create hypoimmune islet cells derived from stem cells. The recent trial at Uppsala University Hospital used modified cadaveric islets for regulatory reasons, demonstrating the viability of the concept. The team transplanted the islets into the brachioradialis muscle in the arm, allowing for non-invasive monitoring using PET/MRI.
Manufacturing these cells at scale presents a significant challenge. Creating a stable, gene-modified master cell bank and ensuring the purity of differentiated stem cells are critical hurdles. Sana hopes to file an investigational new drug (IND) application to start a Phase I trial in 2026.
Vertex Pharmaceuticals: A Parallel Path
Vertex Pharmaceuticals is pursuing a different strategy, using proprietary methods to differentiate pluripotent stem cells into functional pancreatic islets. While their initial approach, zimislecel, still requires immunosuppression, Vertex is also developing its own hypoimmune cell program using gene editing, reflecting a dual strategy to address the needs of patients both now and in the future.
Beyond the Science: Reimbursement and Access
Even with scientific success, challenges remain. The high upfront cost of a one-time curative therapy doesn’t align with existing healthcare reimbursement models. Scaling production to treat the millions living with T1D globally will also require significant investment and infrastructure.
What Patients Value Most
Breakthrough T1D recently convened experts to define patient-reported outcomes for cell therapy trials. Freedom from the daily burdens of T1D – the constant monitoring, calculations, and restrictions – emerged as the most valued outcome. Patients overwhelmingly accept the risks of islet transplantation, even with the need for immunosuppression, highlighting the profound impact of the disease on their lives.
Frequently Asked Questions
- What is islet transplantation? Islet transplantation involves transplanting insulin-producing cells from a donor pancreas into a person with type 1 diabetes.
- Why is immunosuppression necessary after a transplant? The body’s immune system recognizes the transplanted cells as foreign and attempts to reject them. Immunosuppressant drugs suppress the immune system to prevent this rejection.
- What are hypoimmune cells? Hypoimmune cells are genetically engineered to evade immune detection, potentially eliminating the need for immunosuppression.
- What is the current status of gene-edited islet cell therapy? Early trials have shown promising results, but further research and clinical trials are needed before this therapy becomes widely available.
Jo Shorthouse is a freelance science writer from the UK.
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