How Cyclarity is targeting atherosclerosis and giving the body the means to reverse disease from the inside out.
Atherosclerosis is a killer, and while the risk factors can be lowered by healthy lifestyle choices and lipid-lowering agents such as statins, a new approach is needed to address the root-cause of this disease. Cyclarity Therapeutics has developed a new platform aiming to 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: Cyclarity, the company behind the platform, is tackling atherosclerosis by using custom-engineered cyclodextrins to capture, and remove from cells, oxidised cholesterol derivatives. Unchecked, oxidised low-density lipoprotein cholesterol (oxLDL) is taken up by macrophages resulting in a foamy cytoplasmic froth that causes cell death. These dead cells form a necrotic core that can rupture leading to a thrombosis, heart attack or stroke, and if that isn’t dangerous enough, oxLDL triggers an inflammatory response that can grow and loosen those plaques, leading to the same devastating events.
We sat down with Cyclarity’s Vice President of Biology, Dr Daniel M Clemens, to find out more about the company’s lead candidate and how it works.
Daniel Clemens on…
A deadly cycle
Our lead candidate is UDP-003 has been designed to have a specific shape that corresponds to the shape of the oxidized cholesterol that we believe is causing macrophages to become foam cells. Foam cells make up a large part of atherosclerotic lesions and they are also pro-inflammatory cell types, so they, in turn, recruit more macrophages to the site which become inhibited by the 7KC [7-Ketocholesterol] in the plaque. The cycle continues and the plaque grows and grows – until it bursts, causing a heart attack or stroke.
Reversing disease at a cellular level
What we are doing is allowing the body’s cells – your own immune system, your macrophages – to reinvigorate the self-repair mechanism. Macrophages are quite extraordinary cells as they have the capability to do something called phagocytosis, that is to engulf – or eat – other cell types and other types of debris. Normally macrophages monitor the cardiovascular system and vasculature and engulf some of the cholesterol and calcium that’s found there. Once they engulf too much of this oxidized cholesterol they lose their ability to perform phagocytosis, but our experiments in the lab show application of our compound, and therefore the removal of 7KC from these cells, allows them to regain their phagocytic function. Cells that were once pro-inflammatory foam cells – bad guys – are now reinvigorated to be the guardians of your immune system once again, and your body can take apart the plaques in a slow, controlled manner from the inside out.
Casting the cyclodextrin net even wider
Our lead compound goes after 7-Ketocholesterol as its target, but there are other targets that accumulate with diseases of aging. We’re using our platform to engineer next generation versions of our compound and we think that 7-Ketocholesterol actually is the driver of more diseases than only atherosclerosis. There is the potential to go after diseases as wide-ranging as Alzheimer’s, age related macular degeneration, kidney disease, liver disease and stroke.
We think that due to its nature, 7-Ketocholesterol building up over time, over decades, actually is the causative trigger for many of the diseases of aging because it does induce cells into a senescent or quasi-senescent state, and senescent cells are the driver of a great many diseases of aging.