Cyclarity Therapeutics has been processing safety data from a phase 1 safety trial of a cyclodextrin drug to bind 7-ketocholesterol, a toxic form of oxidized cholesterol that contributes to a range of conditions. The company is initially focused on atherosclerosis, the formation of fatty plaques that obstruct blood vessels and ultimately rupture to cause a stroke or heart attack. It is thought that 7-ketocholesterol may be a significant factor in the toxic environment of atherosclerotic plaques, alongside other forms of cholesterol that are also harmful to cell function in larger amounts. Recall that atherosclerosis progresses in its later stages because macrophages are called to the plaque to attempt to repair it, are overwhelmed by the plaque environment, become inflammatory, and die, adding their mass to the plaque. The field is searching for better ways to take the stress off macrophage cells and thus tip the balance towards at least a slower growth of plaque over time.
Data from a study offers the first clinical evidence that 7-ketocholesterol (7KC), a root cause of atherosclerosis, can be safely targeted and removed from the human body, marking a pivotal milestone toward moving cardiovascular treatments from managing arterial damage to achieving true plaque reversal. Results of the phase 1 trial evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of UDP-003. UDP-003 is the first clinical-stage therapeutic discovered using Cyclarity's proprietary drug discovery AI Platform which engineers cyclodextrin molecules to reverse disease and protect against future accumulation of harmful molecules and aging pathologies. These engineered cyclodextrins precisely attract and encapsulate hydrophobic molecules such as forms of cholesterol, rendering them dissolvable in water and thus destined to be purged from the bloodstream.
Most cardiovascular drugs, including statins, anti-inflammatories, and RNA-based therapies, work systemically throughout the body to alter how cholesterol, inflammation, and gene expression are regulated. In contrast, Cyclarity's UDP-003 binds directly to 7KC, a root cause of plaque buildup, then facilitates urinary excretion of it. Much like removing rust from metal, this approach directly targets a key source of damage within plaque with the goal of reversing and preventing atherosclerosis, a primary underlying cause of cardiovascular disease, and does so locally within the plaque to reduce risks of unintended systemic effects.
7KC is considered a biologically active driver of cardiovascular disease, contributing to inflammation, cell death, and plaque instability and has emerged as an important target in emerging therapies aimed at treating the disease at its root. In addition to cardiovascular disease, 7KC is implicated in Alzheimer's disease, metabolic dysfunction-associated steatohepatitis (MASH), and other age-related conditions. Cyclarity is currently enrolling patients with acute coronary syndrome (ACS) into the efficacy cohort of the ongoing Phase 1 trial, which includes pre- and post-treatment coronary CT angiography (CCTA) to assess plaque changes.
View the full article at FightAging
