Type 1 diabetes is an autoimmune disease in which the body's own immune system destroys
the cells in the pancreas—called the beta cells—that make a hormone called insulin
that regulates the blood glucose. Patients today are treated by injecting insulin. Without
insulin, the glucose just builds up in the blood, causes all sorts of damage, and in
the worst case, the cells will starve to death. What we found is that the way that beta cells
are regenerated is not from the expected location. For many years it's been thought that beta
cells regenerated from another structure in the pancreas called the duct. We believed
that also for many years, but when we actually looked carefully, what we found—and this
was published in a paper a few years ago in 2010—was that it was a neighboring cell
in the pancreas, a cell right next to the beta cell called the alpha cell, that makes
a different hormone called glucagon which is related to insulin in controlling blood
glucose and these alpha cells under certain conditions have the ability to turn into beta
cells, a process called transdifferentiation. It's just one cell type turning into another
cell type. So that's what we found in 2010 and what we've doing since then is working
to move that knowledge towards the ability to control it with drugs. So in our most recent
paper I think there are two major things that we accomplished. The first was to replace
the complex surgical procedure that we used in 2010 with a simple peptide so that we can
inject a simple peptide that induces this transdifferentiation or conversion process.
The second thing that we showed in this paper that I think is very important is that we
showed that this transdifferentiation process appears to occur not only in the mice that
we all use as model systems but in humans with type 1 diabetes. The answer to the question
of how to move it into people is that what we need to do is not only develop a targeted
therapy—where we already have made quite a bit of progress—but we need to couple
it, with type 1 diabetes, with an immune therapy so that we prevent the beta cells that we
would cause to be made from being rejected again by this autoimmune process and to that
end we are collaborating with an immunologist at the Institute to work specifically on trying
to induce tolerance, immunological tolerance, to the reformed beta cells. Well our approach
is to generate a very potent population of regulatory T-cells to contain the autoimmune
response that's occurring and one of the ways we are able to do this is to treat the cells
in culture to make them better, stronger, more effective and also we have taken the
approach of injecting antibodies that stimulate these cells in vivo so that they can better
function at the time we inject them. It has been a long road to finding a cure for type
1 diabetes. There is a strong recognition that T regulatory T cells need to be targeted.
In my collaborations with Dr. Levine there are strategies now to induce the differentiation
of those cells from progenitor-like cells or from other endocrine cells in the pancreas
and it is going to be this combination of approaches from the beta-cell biologists and
the immunologists that will be required to achieve a cure.