HRI activators New HRI activators to treat type 2 diabetes mellitus
Diabetes mellitus (DM) is a complex metabolic disorder that has become significantly more common over the last few decades, and already affected 422 million people worldwide by 2014. The increase is mainly due to the rise of type 2 diabetes among younger age groups, such as children and adolescents. As the disease progresses, conventional anti-diabetic oral treatments are not sufficient, and patients have to resort to insulin treatment. This means further oral treatment options need to be investigated.
- To improve the features of a new family of HRI (Heme-Regulated EIF2-alpha kinase) activators, a group of molecules that can be administered orally to treat type 2 DM.
Problem to Solve
Type 2 DM affects around 9% of the world’s population and is one of the most significant economic and healthcare burdens due to its high prevalence and the chronic complications associated with the disease.
Fibroblast growth factor 21 (FGF21) is an anti-diabetic protein that is naturally produced by the liver. FGF21 analogues have been developed to treat type 2 DM, but they need to be administered via subcutaneous injection. This means there is a need to develop oral drugs that can improve the natural production of FGF21 in DM patients.
HRI activators are molecules that increase the levels of the anti-diabetic factor FGF21 in in vitro human liver cells, and in the liver cells of rodents. More specifically, this project focuses on the development of a new HRI activator compound, which has proven to be effective when administered orally to mice fed with a high-fat diet.
Level of InnovationThe oral bioavailability of the new HRI activators offers a competitive advantage in comparison to FGF21 analogues. Moreover, our compound improved some of the metabolic consequences of type 2 DM in a mice model, such as glucose intolerance, fatty liver and hypertriglyceridemia.