Dyslipidemia is an abnormal amount of lipids (e.g. cholesterol and/or fat) in the blood. Most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood, often due to diet and lifestyle. The prolonged elevation of insulin levels can lead to dyslipidemia. Increased levels of O-GlcNAc transferase (OGT) also cause dyslipidemia. Arteria discovered a molecul, which shows promise in fighting dyslipidemia and associated cardiac events. The molecule is called AP-5258 and is highly active in inhibiting the intestinal absorption of lipids.
Diabetic dyslipidemia consists of specifically mild to marked elevation of triglyceride-rich lipoproteins (VLDLs) and VLDL remnants concentrations and low levels of HDL-C. Raised serum triglycerides and low HDL-C often precede the onset of T2DM for many years. In addition, LDL particles are converted to smaller, perhaps more atherogenic, lipoproteins termed ‘small-dense LDLs’. Different mechanisms are responsible for the development of dyslipidemia in individuals with diabetes. Defects in insulin action and hyperglycemia could lead to dyslipidemia in patients with diabetes. In the case of T2DM, the obesity/insulin-resistant state that is at the basis of the development of this disease can in itself lead to lipid abnormalities independently of hyperglycemia.
According to WHO, about 230 million people suffer from Type II diabetes worldwide, which is estimated to rise to 400 million by 2025. Around 40% of type 2 diabetes patients suffer from dyslipidemia, including hypertriglyceridemia. About 19 % of patients who suffer from both hyperglycemia (high blood sugar) and hypertriglyceridemia (high blood fat) suffer from coronary disease.
Dose of AP-5258 molecule fights dyslipidemia and associated cardiac events
Professor Gérard Marguerie, chief scientific officer at Arteria announced obtaining highly promising results...
in preclinical non-regulatory studies for its AP-5258 molecule, an inhibitor of the CD36 receptor. During pre-clinical in vivo tests using a very substantial dose of AP-5258 molecule, the inhibitor demonstrated high intestinal activity, blocking the transfer of postprandial triglycerides.
The oral dose of molecule potentially reduces postprandial hypertriglyceridemia (high blood fat levels of triglycerides after eating) and protects patients from diabetic dyslipidemia. After consuming food, the body produces postprandial plasmatic triglycerides, known as the most powerful markers of cardiac events, particularly amongst diabetic women.
Professor Gérard Marguerie, explains:
“Animal pharmacology and toxicity tests on our AP-5258 molecule are extremely promising. We have been able to link this molecule with a target, the CD36 receptor, identify its mechanism of action and determine the measurable biological parameter, postprandial triglycerides. The fact that we have identified the intestine as the action site of the molecule will enable us to devise and implement an accelerated and simplified development program.”