Christopher Schaaf and Lori Sussel. Diabetes Technol Ther . 2025 Jun;27(6):413-421.

The review article "A Cure for Type 1 Diabetes: Are We There Yet?" by Christopher Schaaf and Lori Sussel, provides a comprehensive overview of advancements in Type 1 Diabetes (T1D) treatment and the ongoing quest for a cure.

Type 1 Diabetes (T1D) is an autoimmune disease where the body attacks insulin-producing beta cells, leading to severe glucose dysregulation. For centuries, T1D was a death sentence, with treatments limited to extreme calorically restricted diets. The history of T1D treatment revolutionized with the discovery and first human use of insulin in 1922 by Banting and Best. This groundbreaking event effectively treated human T1D for the first time. Over 100 years later, insulin therapy remains the standard of care.

Significant successes have been made in T1D management and potential cures:

• Insulin delivery and monitoring have advanced markedly. Most individuals now use insulin pumps for precise dosing and continuous glucose monitors (CGMs) for real-time tracking. Closed-loop systems, where pumps and CGMs communicate, automatically adjust insulin, reducing daily mental burden and increasing the standard of care.
• Islet transplantation has proven effective, notably with the Edmonton Protocol in 2000, allowing some patients to achieve insulin independence.
• Stem cell-based therapies are a promising approach. Vertex Pharmaceuticals’ VX-880 trial, involving transplanted stem cell-derived beta cells, has shown patients achieving A1c levels below 7% without exogenous insulin and producing endogenous insulin. Recently, a patient achieved insulin independence and normal glycemic levels after transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived beta-like cells, although the patient was already on immunosuppression.
• Immune therapies, like teplizumab, have been approved to delay the onset of Stage 3 T1D in adults and pediatric patients with Stage 2 T1D, delaying full insulin dependence.

However, several ongoing challenges hinder widespread clinical application of emerging cures:

• Need for Immunosuppression: Islet and current stem cell transplant therapies require ongoing immunosuppressive regimens to prevent both host-graft rejection and the autoimmune destruction of transplanted cells. These drugs can have significant, detrimental side effects.
• Limited Availability of Donor Tissue: Islet transplant therapies are significantly hindered by a lack of available donor tissue; the Edmonton Protocol, for example, required islet mass from two to four donor pancreata for each transplant.
• Challenges with Stem Cell-Derived Beta Cells: Current differentiation protocols do not produce truly mature, functional beta-like cells that fully recapitulate human beta cell glucose responsiveness, and they result in a mixed population of cells rather than a pure beta-like cell population.
• Limitations of Immunoisolation Devices: Encapsulation devices designed to protect cells often face issues like insufficient oxygen supply to transplanted cells and fibrotic overgrowth.
• Developing Immune-Privileged Cells: Genetically engineering stem cells to be “immune-privileged” is complex; some preclinical strategies have been shown not sufficient alone to protect against rejection in vivo without additional secreted cytokines. These advanced gene-edited therapies are still in early human trials.
• Accessibility and Cost: New therapies will inevitably be expensive, and ensuring their widespread accessibility to everyone who needs it is a critical long-term challenge.
• Patient Skepticism: Decades of unfulfilled promises that “the cure is 5 years away” have led to an enormous amount of disbelief among the patient population regarding reported breakthroughs.

While a functional cure for T1D may still be more than five years away, the remarkable progress in research and therapies means we are closer than ever before, with the ultimate goal being to ensure universal accessibility to such a cure. 

 

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