Advancing gene therapy for low density cholesterol
Coronary artery disease causes around half of all deaths in Europe. Of these, 30 % could be saved by the lowering of low density lipoprotein (LDL) and blood pressure. Another solution is to target HDLs that have many cardio- and vasoprotective functions. Apart from nicotinic acid that is accompanied by significant side effects, currently available drugs for lipid modification have little impact on HDL levels. Due to clinical interest, the 'Functional genomics of inborn errors and therapeutic interventions in high density lipoprotein metabolism' (HDLomics) project aimed to improve diagnostic and prognostic value of the biomarker for HDL cholesterol. Project scientists applied a functional genomics approach including the study of relevant proteins and lipids. This research avenue is particularly promising as research has shown it is the quality of HDL rather than the quantity exerting the atheroprotective effect. Based on genetic data from humans and transgenic mice, increasing the expression of ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes that are responsible for low HDL are possible therapeutic targets. Another candidate for gene therapy is the so-called LCAT for patients with low HDL and apo A-1. On the apo A-1 track again, increased lipoprotein lipase can correct low HDL levels due to alterations in this key gene. Manipulation of HDL levels according to HDLomics project findings is a promising path for future research. Looking further into the genomic future, the HDLomics knowledge base could lead to the development of gene therapy to correct inborn errors of HDL metabolism.
