Promising Drug Candidate Combats Atherosclerosis and Fatty Liver Disease in Large Mammals

A recent study has demonstrated that a novel drug candidate, initially effective in treating severe fatty liver disease, also significantly reduces the development of atherosclerosis in large mammals. Developed at the University of Michigan, this compound, known as DT-109, is a glycine-based tripeptide that limits the formation of atherosclerotic plaques in the aorta and coronary arteries of nonhuman primates. It also prevents vascular calcification, a key factor in arterial stiffening and plaque instability.

The study, conducted in collaboration with Xi'an Jiaotong University Health Science Center and published in Signal Transduction and Targeted Therapy, highlights DT-109’s ability to target multiple pathways involved in cardiovascular disease. Notably, the compound inhibits processes that lead to vascular calcification by reducing signaling from the NLRP3 inflammasome protein, an important mediator of arterial hardening.

Current treatments like statins and PCSK9 inhibitors mainly focus on lowering cholesterol but do not effectively prevent vascular calcification or halt disease progression. In contrast, DT-109 demonstrates a dual-action capability: alleviating liver fat accumulation, as previously shown in 2023 studies published in Cell Metabolism, and addressing the vascular inflammation and calcification associated with atherosclerosis.

The efficacy was observed in nonhuman primates fed a cholesterol-rich diet for ten months before being treated with oral DT-109, which suppressed plaque development and reduced chronic arterial inflammation. These findings suggest that DT-109 could provide a more comprehensive approach to managing cardiovascular risks, especially in patients with metabolic liver disease like NASH, which frequently coexists with atherosclerosis.

Given its promising results, especially in models that closely mimic human disease, DT-109 is positioned as a potential candidate for clinical trials. Its ability to modulate lipid metabolism, reduce liver damage, and prevent arterial calcification presents a significant step forward in the treatment of cardiovascular and metabolic diseases, offering hope for more effective management strategies in the future.

source: https://medicalxpress.com/news/2025-04-drug-candidate-successfully-atherosclerosis-fatty.html