Transcriptomic Therapy for Dyslipidemias Utilizing Nucleic Acids Targeted at ANGPTL3
Gerald F. Watts, Frederick J. Raal, Dick C. Chan
Abstract
Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoprotein metabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndrome and/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70 and 50%, respectively. However, the long-term safety and cost-effectiveness of these agents await to be confirmed in an ongoing and future clinical trials.