Novel heparanase inhibitor could prevent diabetic eye and kidney disease in people with diabetes

Researchers have found in a new study that Novel agent heparanase inhibitor OVZ/HS-1638 may effectively prevent microvascular permeability changes associated with DR and DKD and thereby demonstrating novel systemic approach to address diabetic microvascular complications.

New research has shown a new type of inhibitor drug could prevent microvascular diabetic complications, such as diabetic eye and kidney disease. The University of Bristol-led research is published in Cardiovascular Diabetology.

Diabetes, a disease which results in uncontrolled blood glucose levels, is estimated to affect one in 11 adults worldwide. Even when managed, this common disease can result in life-altering complications, impacting the small blood vessels of the body, known as the microvasculature.

While treatments are available for patients who develop microvascular complications, such as diabetic eye and kidney disease, these treatments do not fully delay progression. Eventually they may result in blindness and kidney failure in patients.

The research team was interested in the protective lining of all blood vessels, called the glycocalyx. This lining is known to be damaged in diabetes. The researchers showed in two mouse models that by preventing damage to this protective layer, the development of diabetic eye and kidney disease could be stopped.

This is achieved using a ‘heparanase inhibitor’. Heparanase acts likes a pair of scissors, damaging the glycocalyx lining. Heparanase inhibitors stop this damage from happening. The research team has developed a novel class of these drugs, which could be successfully developed as a medication to treat patients.

Dr Rebecca Foster, Associate Professor of Microvascular Medicine in the Bristol Medical School: Translational Health Sciences (THS), and senior author of the study, said: “Our findings are exciting as we have shown that one type of medication might be able to prevent different diabetic complications, which is a global health problem for adults living with diabetes.”

Dr Monica Gamez, Research Associate in the Bristol Medical School (THS) and corresponding author, added: “We are currently conducting research to advance our novel class of inhibitors to clinical use. With over 8\% of the global adult population currently living with diabetes, we hope patients could benefit from our findings in the future.”

Reference:

Gamez, M., Elhegni, H.E., Fawaz, S. et al. Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes. Cardiovasc Diabetol 23, 50 (2024). https://doi.org/10.1186/s12933-024-02133-1.