A Drug For Reversing Atherosclerosis Is Ready To Enter Clinical Trials

Cardiovascular disease is the most deadly non-communicable disease in the world. Heart attack and stroke alone are responsible for around a quarter of all human deaths each year. These conditions share the same underlying cause – atherosclerosis, a buildup of fatty plaque (composed mainly of oxidised cholesterol) in the arteries. These plaques may eventually rupture and cause blood clots, blocking off the artery completely and causing a heart attack or stroke.

The growth of fatty plaques is reversible, at least in theory. White blood cells absorb cholesterol and work in tandem with High Density Lipoprotein (HDL) to remove cholesterol from the walls of the blood vessels. Unfortunately, a vicious cycle of chronic inflammation and chemical changes to the cholesterol (in the form of oxidation) causes said white cells to become trapped within blood vessel walls and bloated with cholesterol they cannot process. This problem only worsens with age as chronic inflammation increases. Having a high HDL and a low LDL may slow down plaque growth or even cause it to regress somewhat, but to achieve significant plaque regression we need engineered molecules that can remove modified cholesterol from plaque.

That’s exactly what several biotech companies have been trying to create. Excitingly, one such company – Cyclarity Therapeutics – has recently announced regulatory approval for the first human clinical trial for its compound called UDP-003. UDP-003 is a cyclodextrin – a ring of sugar molecules – that has been engineered to target and remove a specific type of cholesterol called 7-ketocholesterol, which is thought to be particularly important for plaque growth. Dr. Matthew O’Connor, the CEO of Scientific Affairs at Cyclarity, has previously said that UDP-003 might reduce the risk of strokes and heart attacks by as much as 80%. It could even reduce the risk of other diseases in which modified cholesterol plays a role, such as some neurodegenerative diseases and macular degeneration.

This phase 1 trial will include 12 participants, will take place in Australia and will mainly assess safety. While animal trials previously demonstrated safety and showed promise for shrinking plaques, there is no animal model that has as much 7-ketocholesterol in their atherosclerotic plaques as humans, so we don’t know exactly what to expect from these trials. We will keep you updated when those results become available!