“Currently, the bulk of our work has been focused on the BCG arm of the trial, in which our goal is to eliminate the autoreactive “memory” T cells that destroy the pancreatic islets that produce insulin. In our mouse studies, we eliminated the autoreactive memory T cells using one treatment (this is what we are trying to replicate in our current BCG human clinical trials) and used a second intervention to “re-educate” a different population of T cells (“naïve” T cells) so that they would not become autoreactive and attack the insulin-producing islets.
We were able to quickly translate the first arm of treatment from mice to humans because a human-grade equivalent of the drug we used in mice to eliminate the autoreactive cells was known (BCG), available, inexpensive, and generally accepted as safe with an 80+-year history of clinical use. Because of these factors, BCG has the potential to more rapidly become available in the clinic if it is successful and has therefore been the focus of our efforts. We believe that even just this one limb of therapy will have clinical benefits in diabetic patients.
The second arm of our study will require more preclinical work before it can be translated efficiently and affordably to human testing. This research will be more costly than the BCG research, and may even require that we develop a new drug. In our mouse experiments, we re-educated the naive T cells by transplanting cells from a non-diabetic mouse donor into the diabetic mice. The transplanted cells correctly expressed a molecule called “MHC Class I and self-peptide,” which means that they would not mistakenly attack the insulin-producing islets.
While the use of cells from “normal” donors (i.e. donors without type 1 diabetes) is a possible therapeutic option in humans, we are seeking alternative strategies—such as therapies that do not rely on donor cells—that would allow more rapid, less expensive, safer clinical trials. We hope that we will be able to find these alternative methods and achieve the goal of re-educating the naïve T cells of humans.
In 2005 and 2006, we received an initial grant to screen compounds that may be effective as the second limb of treatment. This funding allowed us to perform experiments in diabetic animals and identify some possible chemical/drug candidates that might help us re-educate cells within the MHC class I and self-peptide pathway. Within this basic science program, we are trying to identify an inexpensive solution for the second intervention, similar to what we have done with BCG, since we have learned that this generic drug approach allows us to move quickly and safely into the clinic. However, if we were to receive significant funding for new drug development, we would of course pursue the development of a new drug based on our initial project that screened potentially effective compounds. We have not yet identified a source for that funding, since a new drug costs about $1 Billion to develop! ”