Grant: Project Grant

Excess fat (cholesterol) deposits in our blood vessels can lead to heart disease. The blood vessel wall is made up of special proteins that contain sugar molecules with sticky regions that specifically attach and trap the cholesterol-carrying particles circulating in our blood. Current treatments aim to reduce the amount of cholesterol (e.g LDL or bad cholesterol) in the blood stream. There is currently no drug (available or under research) that can specifically target the blood vessels to reduce the accumulation of cholesterol. We have collaborated with the Centre for Molecular Immunology in Cuba, that are experts in developing vaccine like drugs. They have recently developed a compound (antibody) called 'chP3R99' that has two fold action: (i) It specifically binds to the sugar chains which prevents the cholesterol from attaching to blood vessels (ii) This antibody has vaccine-like properties, which means it does not have to be injected repeatedly to maintain its effect. Once injected it can continue to produce similar antibodies and reduce the overall cost of the therapy. Diabetes increases the risk for heart disease. There are two types of bad forms of cholesterol in our blood (i) Traditional bad cholesterol (LDL) produced from the liver and (ii) 'Remnant' cholesterol, derived from diet and secreted by the intestine. During diabetes, remnant cholesterol is often increased while the LDL cholesterol can remain normal. Therefore the aim of this project is to determine if the novel antibody 'chP3R99' can reduce the accumulation of remnant cholesterol as well as LDL cholesterol in blood vessels of animal models that have diabetes. We also have a collaboration with a cardiologist who can provide us with donor (discarded) human blood vessels and other tissues. We propose to use donor blood vessels to circulate remnant cholesterol with/without the antibody chP3R99 to assess the extent that we can reduce cholesterol build up in human tissue.