Regeneration Research Strategy
In contrast to replacement of beta cells using outside sources of cells, which involves a surgical transplant procedure, internal regeneration of beta cells has the potential to restore beta cell function in large numbers of individuals using drug-based approaches. JDRF has prioritized funding of beta cell regeneration to catalyze gap-addressing research and development. Within the field of beta cell regeneration, the research areas of growing beta cells from precursor stem cells, proliferation of residual or newly generated pancreatic beta cells, reprogramming of other cell types (liver, acinar, alpha cells) into beta cells, and targeting survival of residual or newly generated beta cells are all priorities.
The primary goal of the program is to support translation of research toward clinical evaluation, while continuing to support discovery research to identify and validate novel targets and pathways for beta cell regeneration. JDRF is uniquely filling a critical scientific gap by supporting efforts to identify cell targets, validate drug targets and pathways, create new animal models of regeneration, develop biomarkers, as well as supporting proof-of-concept clinical studies. We have a specific interest in better understanding the mechanisms underlying normal times of beta cell expansion (such as in pregnancy or obesity) to identify safe and physiologically relevant targets to promote beta cell regeneration because therapeutic safety will prove of paramount importance.
Improved abilities to detect and measure changes in beta cell stress, destruction and regeneration will be useful both as predictive markers for type 1 diabetes as well as markers of the effectiveness for therapeutics aimed at reducing beta cell stress and destruction or promoting beta cell regeneration. To date, there has been a lack of specific markers for stressed or regenerated beta cells. For beta cell mass and function, the location of the pancreas, the relatively small volume of the pancreas that is comprised of beta cells (<2%), and the requirement to distinguish beta cells from other cells of the islets make assessment a particular challenge. Imaging agents are needed that are specific for the beta cell or its function, and which do not damage the beta cell, initiate an immune response, or involve substantial radiation exposure, since the procedure should be safe for children and useful repetitively.
Regeneration Research: Top Priority Areas for Fiscal Year 2013
- Advancing basic research to target validation and drug discovery stage for beta cell survival and regenerating therapies.
- Islet cell plasticity and alpha cell to beta cell conversion.
- Targets and therapeutic strategies to simultaneous promote beta cell survival and reduce inflammatory responses in the islet.
- Imaging technologies for non-invasive quantitative measurement of beta cell mass, function, inflammation, rejection, death, and newly generated beta cells and their late-stage precursors.
- Site-targeted delivery of therapeutics to pancreatic islet endocrine cells.