At the April 2014 JDRF-GNF (Genomics Institute of the Novartis Research Foundation) meeting, Dr. Byran Laffitte described how GNF has the potential to identify the first disease altering therapy for T1D. He presented preclinical evidence that GNF has identified the first highly effective low molecular weight regulators of beta cell proliferation. Overall, GNF has identified five novel beta cell proliferators using this technique, two of which he discussed: GNF4156 and GNF4877. These preclinical agents have been found to robustly stimulate rat and human beta cell proliferation in islets. This leads to an expansion of human islet mass with the retention of their function. In rodents, these candidates have also been associated with an improvement in glucose tolerance. These potential drugs work by inhibiting an enzyme called DYRK1a, which is thought to play a significant role in a signaling pathway regulating cell proliferation. Studies to confirm these findings are underway. (Close Concerns, April 23, 2014)
A beta cell regeneration therapy requires the presence of some remaining beta cells in people with T1D. The JDRF- funded Medalist study several years ago first identified the presence of such residual beta cells in people with T1D for as long as 50 years after a T1D diagnosis. Now, several recently published (non-JDRF funded) reports have confirmed these findings and showed that most patients with long- duration T1D continue to secrete very low levels of natural insulin, which increase after meals (see independent work of Drs. Oram, Faustman, Greenbaum for details). This is consistent with the presence of a small number of still functional beta cells and implies that some beta cells are either escaping immune attack or undergoing some form of natural regeneration. These findings strengthen the hope for the potential for novel regeneration therapies to positively impact the course of T1D.