Type 1 diabetes (T1D) is a chronic autoimmune condition where the body’s immune system mistakenly targets and destroys the insulin-producing beta cells within the pancreas. This destruction results in a near-total inability to produce insulin, the hormone necessary to regulate blood sugar, leading to lifelong dependence on external insulin administration. While modern technology like continuous glucose monitors and insulin pumps has significantly improved daily management, the need for constant monitoring and the risk of long-term complications remain. Research aims for a definitive cure, which involves either replacing the destroyed cells or stopping the immune attack that caused the damage.
Cell Replacement Therapies
Cell replacement therapies focus on addressing the result of T1D—the lack of functional beta cells—by introducing new, insulin-producing cells into the body. The most promising avenue involves pluripotent stem cells, which are cells capable of developing into nearly any cell type, including the desired insulin-secreting beta cells. Researchers have developed sophisticated protocols to guide these stem cells to differentiate into fully functional islet cells in a laboratory setting, creating a potentially unlimited and scalable source of replacement cells.
One advanced clinical program, using stem cell-derived islet cells, has demonstrated success in early-stage trials, with some participants achieving insulin independence for over a year. However, because the body’s autoimmune system is still active, these transplanted cells are vulnerable to the same destruction as the original ones. Consequently, patients receiving these cells currently require chronic immunosuppression drugs to prevent their immune system from attacking the new cells, which limits the therapy’s widespread use.
An area of research is the development of encapsulation technologies to shield transplanted cells from the immune system. These methods involve placing the beta cells inside a protective barrier or device that allows nutrients and insulin to pass through but blocks immune cells from reaching the graft. Encapsulation devices are designed to create immunoisolation, eliminating the need for general immunosuppression and its associated risks. Researchers are developing micro- and macro-scale devices using biocompatible materials to ensure cell survival and prevent the formation of scar tissue.
Halting the Autoimmune Process
Immunotherapy focuses on addressing the root cause of T1D: the misguided attack by the immune system. These treatments aim to modulate the immune system to stop destroying the beta cells while leaving the body’s ability to fight infections intact. One well-studied class of agents is the anti-CD3 monoclonal antibodies, such as teplizumab, which target T-lymphocytes, the immune cells responsible for the destruction.
The use of anti-CD3 antibodies has shown success in clinical trials, particularly in delaying the onset of T1D in individuals at high risk. When administered in the early stages of the disease, these antibodies can preserve remaining beta cell function, measured by C-peptide levels. The therapy works by temporarily modulating the T-cells, which results in the generation of regulatory T-cells that help suppress the autoimmune reaction.
Treating T1D involves two distinct challenges: prevention before symptom onset and reversal after diagnosis. For prevention, the goal is to induce long-term immune tolerance without requiring continuous drug administration. In newly diagnosed patients, the aim is to halt the destruction and preserve residual insulin production. The main hurdle is developing a therapy that achieves long-term, specific immune tolerance to the beta cells without broadly suppressing the entire immune system, which is necessary to avoid serious side effects.
Assessing the Proximity to a Cure
Progress toward a cure is best understood by distinguishing between two goals: a “functional cure” and a “sterilizing cure.” A functional cure means a person can achieve near-normal blood sugar control and be independent of external insulin administration, often requiring some degree of ongoing intervention. A sterilizing cure would involve completely eradicating the autoimmune threat and fully restoring normal beta cell function without any need for medication or devices.
Based on current clinical trial data, a functional cure is significantly closer to reality than a sterilizing cure. The most promising cell replacement therapy, Vertex Pharmaceuticals’ zimislecel (formerly VX-880), has progressed to a Phase 1/2/3 trial, showing that a high percentage of recipients achieved insulin independence. The therapy, however, still requires patients to take immunosuppression drugs, making it a functional, but not sterilizing, cure.
In the realm of immunotherapies, teplizumab, an anti-CD3 antibody, is already approved for delaying the onset of Stage 3 T1D. This drug has completed Phase 3 trials and represents a breakthrough in disease modification, showing that the autoimmune process can be successfully intercepted. Other immunomodulators and combination therapies are moving through Phase 2 and Phase 3 trials, aiming to improve this initial success and extend benefits to those already diagnosed.
The convergence of these two approaches—cell replacement and immunomodulation—is likely where the first widely accessible cure will emerge. Combining stem cell-derived beta cells with a protective device or gene-editing technology could eliminate the need for general immunosuppression. Optimistic timelines suggest that a functional cure, likely involving a stem cell product or advanced immunomodulation, could be commercially available within five to seven years, provided current late-stage clinical trials continue to demonstrate long-term safety and efficacy.