• Daniel Gaudet and Diane Brisson.
• Lipidology Unit, Community genomic medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21, Chicoutimi, Quebec, Canada.
• Curr. Opin. Lipidol. 2015 Dec 1; 26 (6): 553-65.

Purpose Of ReviewGene-based therapies are designed to modulate gene expression in specific tissues by introducing into cells transgenes, antisense oligonucleotides, RNA interference, microRNAs, or a variety of other oligonucleotide-based compounds and their delivery systems. Several types of gene-based therapies are already available or in clinical development to treat severe lipid-related disorders and associated risk. The review briefly presents the current status and future challenges of these therapies in clinical lipidology, focusing on most advanced and promising agents or mechanisms.Recent FindingsGene-based agents address several unmet medical needs in lipidology such as homozygous familial hypercholesterolemia, familial or multifactorial chylomicronemia, severe hypertriglyceridemia, elevated lipoprotein (a), familial partial lipodystrophy, nonalcoholic fatty liver disease, and hypoalphalipoproteinemia. Most advanced antisense oligonucleotide drugs target apolipoprotein C-III, apolipoprotein (a), angiopoietin-like 3, and diacylglycerol o-acyltransferase-2. Long-term efficacy and safety data are now available for two gene-based agents, mipomersen, approved in the USA for homozygous familial hypercholesterolemia and Glybera, AAV1-LPLS447X gene therapy, conditionally approved in Europe for lipoprotein lipase deficiency.SummaryAlthough positive to date, the overall benefit-risk ratio of gene-based therapies is yet to be documented long term across additional patients and conditions. The next generation of such therapies might improve their therapeutic index.

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