Key result
Gene-based therapies promise to transform lipid management via infrequent dosing and high target selectivity.
Why the study?
Many patients do not achieve guideline-recommended lipid levels with currently available therapies, and specific Lp(a) lowering agents are not available, driving the search for novel targets and treatment modalities.
Gene-based therapies offer a promising paradigm shift in lipid management by enabling the targeting of previously undruggable pathways like Lp(a) with low dosing frequency.
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Gene-based lipid therapies warrant caution before clinical adoption; leaves open their role pending randomized trials.
INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. High plasma low-density lipoprotein cholesterol (LDL-C) levels are a key CVD-risk factor. Triglyceride-rich remnant particles and lipoprotein(a) (Lp[a]) are also causally related to CVD. Consequently, therapeutic strategies for lowering LDL-C and triglyceride levels are widely used in routine clinical practice; however, specific Lp(a) lowering agents are not available. Many patients do not achieve guideline-recommended lipid levels with currently available therapies; hence, novel targets and treatment modalities are eagerly sought. AREAS COVERED: We discuss the milestones on the trajectory toward the full application of gene-based therapies in daily clinical practice. We describe the different methods, ranging from antisense oligonucleotides to liver-directed gene therapy and Crispr-cas9 modification to target the pivotal players in lipid metabolism: PCSK9, APOB, ANGPTL3, Lp(a), LDLR, and apoC-III. EXPERT OPINION: While acknowledging their different stages of development, gene-based therapies are likely to invoke a paradigm shift in lipid management because they allow us to target previously undruggable targets. Moreover, their low dosing frequency, high target selectivity, and relatively predictable adverse event profile are considered major advantages over current lipid-lowering therapies.
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Tromp et al. (2020) conducted a review in Cardiovascular disease and dyslipidemia. Gene-based therapies (antisense oligonucleotides, liver-directed gene therapy, Crispr-cas9) was evaluated. Gene-based therapies targeting lipid metabolism are likely to invoke a paradigm shift in lipid management due to their low dosing frequency, high target selectivity, and predictable adverse events.
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