Seattle, WA — February 02, 2023, A paper published today in the peer-reviewed journal Nature Communications, co-authored by researchers from Columbia University, Kayothera, Inc., and Princeton University, describes a new therapeutic strategy for treatment of type 2 diabetes (T2D) by targeting the enzyme Aldehyde Dehydrogenase 1A3 (ALDH1A3). The research, titled “Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β cell failure,” demonstrates a pathway for reversing β cell dysfunction, which is the key cause of T2D.
The study resolves two significant questions in diabetes research: 1) can diseased β cells be restored to healthy function and (2) whether the activity of ALDH1A3 is just a marker or if it directly contributes to β cell failure. The authors show that ALDH1A3-positive β cells can be converted back into functional, mature β cells using unique lineage tracing tools developed at Columbia University. This data suggests that no matter how severe, T2D can be reversed through β cell regeneration. Next, by using both genetic models and Kayothera’s innovative ALDH1A3 inhibitors, the paper demonstrates that ALDH1A3 inhibition can regenerate healthy β cells in both diabetic mice and, importantly, in β cells derived from human type 2 diabetic patients. The findings indicate that inhibiting ALDH1A3 offers a promising new therapeutic approach for T2D with important disease modifying potential.
“Our work demonstrates that targeting ALDH1A3 can restore the function of insulin-producing β cells, a novel concept with immense therapeutic potential,” said Thong Le, CEO of Kayothera, Inc. “The use of our innovative ALDH1A3 inhibitors was critical to these findings, confirming that this approach holds promise for significant disease modification in diabetes.”
Mark Esposito, Ph.D., a co-author and founder of Kayothera, Inc., added, “The findings published in Nature Communications are a critical step in our mission to develop first-in-class therapies for metabolic diseases. By inhibiting this key enzyme, we believe we can not only manage but potentially reverse the cellular dysfunction at the root of type 2 diabetes.”
About the Publication
The paper is available online in the journal Nature Communications.
Title: Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure
Authors: Jinsook Son, Wen Du, Mark Esposito, Kaavian Shariati, Hongxu Ding, Yibin Kang, and Domenico Accili.