RESEARCH PATHWAYS

A Practical Cure focuses on outcomes, not research pathways. In the pursuit of a Practical Cure there is no bias for or against particular research types or methods. Any research project that has the potential to deliver the characteristics of a Practical Cure is welcome.

While reversing type 1 diabetes would be ideal, a Practical Cure is broad enough to accommodate periodic treatment or maintenance therapy. As a result, a Practical Cure initiative draws in a wide set of possible pathways and projects.

There are currently four broad research pathways in development that could yield a Practical Cure. While each of the four approaches has the potential to deliver a Practical Cure by itself, it is also possible that a full solution will require a combination of elements from different pathways. The four pathways are:

I. Islet Cell Transplantation

This pathway refers to transplanting insulin-producing islet cells into a person with type 1 diabetes. Islet cell transplantation requires a sustainable and widely-available supply of islet cells. Historically, cadavers have been the only proven source of insulin-producing cells, but they have very limited availability. In search of a more readily available source, researchers have tried to use islet cells from animals, particularly pigs, with only limited success. More recently, there have been advances toward deriving a sustainable cell supply from human stem cells.

Islet cell transplantation also requires a solution to protect the cells from the immune attack after they have been implanted in the body. The primary approach to protection has been encapsulating islet cells in an implantable device that acts as a physical barrier between the islet cells and the immune attack. Despite considerable time and energy, various encapsulation approaches have been tested with no breakthrough. However, advances in biomaterials have given rise to a new round of encapsulation work.

II. Device that Mimics the Pancreas

This type of device, sometimes referred to as an artificial pancreas, is under development at several commercial entities and academic research centers, but most are not advanced enough to deliver a Practical Cure. To be a Practical Cure, a mechanical device that mimics the pancreas would require an exceptionally reliable closed-loop system that is adaptive to each individual.

III. Glucose-Responsive Insulin (aka Smart Insulin)

Colloquially referred to as smart insulin, the intent of this pathway is to chemically engineer an insulin that is “smart” in the sense that it is activated only in response to rises in blood glucose levels. It would be injected subcutaneously and remain inactive until chemical compounds in or around the insulin sense that blood glucose has risen above a certain level. At that point, the smart insulin would quickly kick in to bring glucose levels down. The smart insulin would automatically become inactive again once blood glucose reached a normal level, thus avoiding low blood sugar. While there is considerable enthusiasm for this project in the T1D community, only one of the research efforts has entered human trials.

IV. Modifying the Immune System

Stated simply, this pathway stops the body’s immune system from attacking the insulin-producing beta cells. There are three basic approaches:

1. Blocking

A direct way to stop diabetes is to stop the autoimmune attack. This would include any approach that blocks the autoimmune attack without reducing the body’s ability to fight disease and infection. In order for this to be a Practical Cure for established type 1 diabetics, there would have to be a sufficient amount of beta cells still in the body that could multiply and produce a sufficient amount of insulin after the attack was blocked. There is some evidence that even people with long-standing T1D have residual beta cells left, but if this is not the case, blocking the autoimmune attack would need to be combined with islet cell transplantation.

2. Balancing

Some researchers believe that T1D exists because the immune system has become unbalanced, meaning either the body is making too many killer T-cells which fight disease (and attack beta cells in type 1), or too few regulatory T-cells to keep the killer cells in check. Balancing the immune system would involve any approach that restores balance between killer T-cells and regulatory T-cells. To date there has only been limited progress along this path. Additionally, this approach faces the same islet cell supply issues as blocking.

3. Retraining

 It may be possible to retrain the immune system not to attack beta cells. These approaches take immune system cells in the blood and retrain them not to attack the islet cells, either by ongoing exposure therapy (potentially through periodic injections) or by a mechanized process that removes, treats, and reinserts immune system cells in the blood.