August 19, 2025
This report covers the three major research platforms to a Practical Cure, and the seven pathways to get there. JDCA revises these each year, incorporating feedback from the T1D community. This year, we integrated new community survey findings regarding the most controversial pathways.
The three major platforms remain the same:
- Cell Supply Solutions
- Cell Protection Solutions
- Advanced Insulin Delivery Solutions
Each platform contains two or more pathways—like the branches of a tree—to achieve a Practical Cure. Note that a full Practical Cure will likely contain multiple pathways.
The most controversial platform based on community feedback is Advanced Insulin Delivery Solutions, which includes glucose-responsive insulin and the advanced artificial pancreas. JDCA fielded a survey last month to determine whether the community felt these should be retained. Interestingly, results indicated that the T1D community’s opinions were divided in a near 50/50 split. In the Advanced Insulin Delivery Solutions section of this report, we share more detailed results.
Cell Supply Solutions
This major research platform intends to restore the insulin-producing beta cells destroyed by the autoimmune attack. The two pathways to this end are described below.
1. Cell Replacement
This pathway directly replaces the lost insulin-producing cells with new ones, often through a procedure called islet cell transplantation. The main cell sources for this approach are:
Stem Cell-Derived Beta Cells (sBCs): Islets are lab-grown from human stem cells. They are gathered from adult or embryonic tissue and sourced from another person (allogeneic) or from one’s own body (autologous). Allogeneic cells can be produced at scale, enabling wider access, whereas autologous cells are developed on a person-to-person basis. There has been considerable progress along this route over the past five years.
Xenogeneic Cells: These are derived from non-human animals, most commonly pigs. Though nearly unlimited in supply and inexpensive to procure, they face a heightened immune reaction.
Transdifferentiation: Non-insulin-producing cells are transformed into beta-like cells. In this approach, mature cells are directly changed into mature beta-like cells. Long-term functionality and survival of beta-like cells are major hurdles.
2. Cell Regeneration
This pathway attempts to reawaken and encourage the reproduction of latent beta cell mass that persists in the body even after decades of living with T1D. This approach has achieved some successes in stimulating small amounts of c-peptide growth but remains far from insulin independence.
Cell Protection Solutions
This major platform aims to prevent the immune system from attacking insulin-producing beta cells by either stopping the attack or by hiding cells from the attack. There are three methods to achieve this goal.
1. Encapsulation
This pathway hides insulin-producing cells from the immune system with a physical barrier. All encapsulation devices have a semi-permeable surface designed to stop immune cells from entering, while allowing oxygen and nutrients in (to keep cells alive), and letting insulin out. This method has been explored for decades, but none have been successful. There are three types of encapsulation devices.
- Macroencapsulation: Many islets in one large device.
- Microencapsulation: As few as one to two islets in a small device.
- Nanoencapsulation: One islet coated in a protective, gel-like layer.
2. Immune-Evasive Beta Cells
This pathway primarily uses gene-editing techniques to alter the DNA of insulin-producing beta cells, hiding them from the immune system. This method is gaining momentum with researchers and has seen some early positive results in T1D.
3. Immune System Modification
The immune system's attack on beta cells is turned off at its root. A wide variety of methods and targets are being investigated to accomplish this goal. This may include manipulating system checkpoints, altering cell interaction, editing the genes of immune cells, inducing beta cell tolerance, and others.
These methods may result in suppressing the immune response in a localized manner around beta cells. Full-body immunosuppression is not included in this pathway, as it impacts the entire immune response, posing serious adverse risks that are unacceptable to the majority of the T1D community (greater risk of infection, cancer, liver toxicity, etc.).
Advanced Insulin Delivery Solutions
This major platform intends to fully automate insulin delivery and maintain normal glucose levels. There are two pathways working toward this objective.
At JDCA’s foundation, we fielded surveys to the T1D community to define the requirements of a Practical Cure and the pathways to get there. At the time, responses for Advanced Insulin Delivery Solutions were clear-cut: Hope was fresh, and it had validity. Today, with admittedly little movement in this research area, community sentiment is almost split down the middle. Though advancements have been made in alternative forms of insulin and improvements in closed-loop technology, we are still far from glucose-responsive insulin or an advanced artificial pancreas.
The latest survey received over 500 responses from members of the T1D community, composed of family members, friends, caregivers, and those living with the disease today. These surveys are vital to ensure the contemporary Voice of the Donor is heard and appropriately reflected.
1. Glucose-Responsive Insulin (GRI)
Also known as ‘smart insulin,’ GRI is designed to release insulin only when blood glucose rises above the normal range, automatically controlling blood sugar without the risk of hypoglycemia. There are several delivery methods being explored, such as an injection, oral pill, or patch.
In the survey, 6/10 respondents believe a GRI qualifies as a Practical Cure. They note, however, that GRI must be effective and seamless to manage.
2. Advanced Artificial Pancreas (AAP)
AAP is any device that mimics the glucose-regulating functions of a healthy pancreas and is fully automated, fully dependable, and low profile. Dual hormone, it delivers both glucagon and insulin. In general, it must be small enough to ‘set it and forget it.’
Overall, 54% of survey respondents said that an AAP qualifies as a Practical Cure. At the same time, 1/3 held the steadfast belief throughout that an AAP—or any device—should not be considered a Practical Cure. JDCA recognizes and respects these strong points of view, but given the majority viewpoint (albeit a small one), will keep AAP as a Practical Cure pathway for the foreseeable future or until sentiment shifts.
