2015 State of the Cure, the fourth annual edition of this report, which
takes stock of the past year’s progress toward a Practical Cure for type 1 diabetes.
'At this time, there are four broad research pathways that have the potential to result in
a Practical Cure within the next 15 years. While each pathway has the potential to deliver
a Practical Cure on its own, it is also possible that a complete solution will require
a combination of multiple pathways.
THE FOUR PRACTICAL CURE PATHWAYS:
1. Islet Cell Transplantation involves implanting insulin-producing islet cells into a person
with type 1 diabetes. It has three major components:
• Cell protection: The islet cells must be protected from immune attack after they
have been implanted in the body. Various encapsulation approaches have been
tested in humans with no breakthrough to date. Immune-suppressing drugs are
another alternative, but current side effects would have to be reduced to qualify
as part of a Practical Cure.
• Cell supply: The only existing source of Islet cells is cadavers, which have very limited
availability. Only about 100 islet cell transplantations can be done annually in
the United States due to limits in cell supply. Research into deriving a sustainable
supply from human stem cells has seen recent advances. Two well known examples
of cell supply research are Viacyte’s work with progenitor cells, currently in
human trials, and Douglas Melton’s work at Harvard University, which produces
beta cells from an embryonic stem cell line but is several years away from human
• Site selection: Islet cells require large supplies of oxygen and nutrients to survive.
The current protocol is to transplant islet cells into the liver, where the majority do
not survive. Other transplantation sites, including the stomach lining and the area
under the skin, are being tested as alternatives.
2. Immune System Modification would use drugs or treatments to stop the body’s
immune system from attacking the insulin-producing beta cells. There are three modification
approaches: 1) blocking, 2) retraining, or 3) balancing. Blocking would most
likely use a drug to stop the autoimmune attack. Retraining refers to approaches that
seek to correct the autoimmune response, for example, through exposure to properly
functioning T Cells. Balancing seeks to restore a healthy ratio between the immune system’s
Killer T cells and Regulatory T cells. To date, there has been only limited progress
along this pathway.
3. Glucose-Responsive Insulin, aka “smart insulin,” is chemically activated in response
to changes in blood glucose. Once injected under the skin, “smart insulin” acts as a
biological artificial pancreas, maintaining even blood sugars with no other intervention
required. Insulin is bound to a protein structure that acts as a gate for insulin release,
closing when blood sugar is low and opening as blood sugars rise. To qualify as a Practical
Cure, smart insulin would have to last long enough to require no more than a single
injection per day. Additionally, the risks of having excess insulin (present but not yet
activated) in the body must be well understood. The best known example of this pathway
is the Merck project, which has been in human trials for over a year, but utilizing
a study design that still needs multiple injections per day. In the current study format,
it does not yet fulfill the Practical Cure vision but we are hopeful that it will iterate and
progress. We will address any changes to this outlook in future reports.
4. A Device that Mimics the Pancreas, often referred to as an artificial pancreas, is under
development at several commercial and academic centers. To be a Practical Cure,
a device that mimics the pancreas would require an exceptionally reliable closed-loop
system that adapts to each individual. It also must be small enough to be forgotten
about. The most well know projects are the Artificial Pancreas work led by JDRF and
the Bionic Pancreas work led by Ed Damiano at Boston University. Progress on the
devices has been encouraging with some excellent results in human trials. However,
several important hurdles remain, including a proven shelf-stable glucagon, adequate
fail-safe back-up systems, and a device size that is truly small enough to be worn without