ATHEROSCLEROSIS

Atherosclerosis is the chronic build up of plaques within your artery, which are composed of cholesterol, fats, inflammatory cells and other substances. The growth of plaques leads to thickening or hardening of the artery and they can end up causing heart attack, stroke, and peripheral vascular disease. Atherosclerosis is the leading cause of death globally.

Medical needs

Clinically, the most successful approach to manage atherosclerosis is to lower blood low-density lipoprotein-cholesterol (LDL-C) level using statins. However, even though statin therapy can reduce the risk of clinical events by ~30%, the majority of patients (~70%) still suffer from residual risk. Many patients on statin therapy have clinical events despite successful reductions in LDL-C. Some patients do not respond to statin therapy, failing to achieve low LDL-C level. Therefore, the development of new treatment options that can be used in addition or alternatively to standard care will be crucial to further reduce the residual risk.

Mechanism of action

MoA atherosclerosis_edited.png

Whereas statins primarily work in the liver by increasing the LDL-C receptor thereof and reducing LDL-C level in the blood, cyclodextrin can directly remove cholesterol from atherosclerotic plaques. It has been demonstrated that cyclodextrin reduces cholesterol content, reprogram macrophages to promote cholesterol efflux, and exert significant anti-inflammatory effects within plaques. RN-005 exhibits excellent efficacy in solubilizing free cholesterol and inducing cholesterol efflux by macrophages. Having a different mechanism of action from statin and low toxicity, RN-005 will provide a novel and safe treatment option for patients with atherosclerosis.

References

- Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming (Science translational Medicine, 2016)

- Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity (Journal of Controlled Release, 2020)

- Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy (ACS Nano, 2020)