Key result
Gene-based therapies, including mipomersen and Glybera, are available or in development for severe lipid-related disorders, though long-term benefit-risk ratios require further documentation.
Gene-based therapies represent a promising approach for severe lipid disorders, though long-term safety and efficacy data are still needed.
Requires additional long-term data before adoption; leaves open the benefit-risk balance for gene-based lipid therapies.
PURPOSE OF REVIEW: Gene-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 FINDINGS: Gene-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. SUMMARY: Although 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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Gaudet et al. (2015) conducted a review in severe lipid-related disorders. Gene-based therapies was evaluated. Gene-based therapies, including mipomersen and Glybera, are available or in development for severe lipid-related disorders, though long-term benefit-risk ratios require further documentation.
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