Constructively disruptive – tackling atherosclerosis through disease reversal

Cyclarity CEO talks tackling oxidised cholesterol and taking on the world’s biggest killer.

Cyclarity Therapeutics is on a mission to develop technology to treat, cure and reverse atherosclerosis. The company’s tech, rationally-designed cyclodextrin molecules that remove arterial plaque by clearing the non-degradable oxidised cholesterol that accumulates within cells in the arterial walls, could make a significant dent in cardiovascular disease’s ranking as the world’s number one killer by reducing incidences of heart attack and stroke.

Longevity.Technology: Michael Kope, who was also Founding CEO of SENS Research Foundation, is the Co-Founder and Co-CEO of Cyclarity Therapeutics. Cyclarity is spearheading true disease-modifying treatments for age-related diseases and doing it with simple and direct interventions, so we were delighted to catch up with Michael and discuss his biotech company and its work.

Mike Kope on…

ABC (atherosclerosis because cholesterol)

We always knew that atherosclerosis was a special case; it’s by far the world’s biggest killer and atherosclerosis may be one of those rare situations where an age-related disease is being driven primarily by a single-point cause – basically, the failure of the cardiovascular self-repair system once it gets overloaded with molecules that it cannot properly process. The most toxic of these are forms of oxidised cholesterol in the cardiovascular system.

From hero to villain…

We have a pretty robust cardiovascular system at work in all of us – macrophages are being recruited to the site of an injury, they pick up detritus and particles and help to clean up our arteries. But when they get overloaded with cholesterol derivatives that have been oxidised, their lysosome can no longer function, and they explode from healthy firemen cleaning up the cardiovascular system into arsonists that become these foam cells, sort of quasi-senescent cells that become the necrotic core of an atherosclerotic plaque. This triggers all sorts of inflammaging responses, and eventually a rupture and the event that causes a heart attack or stroke.

…and back again – the fascinating science of disease reversal

Most of what’s going on right now is lipid management – amelioration of cholesterol or triglycerides using statins or PCSK9 inhibitors. But we want to work underneath the driver of when the cholesterol becomes oxidised and starts to defeat the repair system.

Our lead candidate UDP003 is a dimerised and specially-formed cyclodextrin molecule that we created with a combination of computational analysis and synthetic bench chemistry. We call it constructively disruptive, because there’s nothing about this drug that requires an immediate challenge to standard of care. If you’re on statins, stay on statins! But we can also put you on our drug, look at your oxidised cholesterol levels and see if we can do something about that – the standard of care does not need to be disrupted, and hopefully we can demonstrate that a reversal approach, as opposed to an amelioration approach is going to be much, much more effective in saving lives.