Cellular and Molecular Aspects of Managing Familial Hypercholesterolemia: Recent and Emerging Therapeutic Approaches

Forough      Taheri; Eskandar      Taghizadeh; Fatemeh      Baniamerian; Daryoush      Rostami; Ahmad      Rozeian; Seyed      Mohammad Gheibi hayat; Tannaz      Jamialahmadi; Željko      Reiner; Amirhossein      Sahebkar
Abstract

Familial hypercholesterolemia (FH) as a high-frequency genetic disorder is diagnosed based on family and/or patient’s history of coronary heart disease (CHD) or some other atherosclerotic diseases, LDL-C levels, and/or clinical signs such as tendinous xanthoma, arcus cornealis before age 45 years as well as a functional mutation in the LDLR, apoB or PCSK9 gene. Its clinical features are detectable since early childhood. Early diagnosis and timely treatment increase life expectancy in most patients with FH. Current FH therapies decrease the level of lowdensity lipoprotein up to ≥50% from baseline with diet, pharmacotherapeutic treatment, lipid apheresis, and liver transplantation. The cornerstone of medical therapy is the use of more potent statins in higher doses, to which often ezetimibe has to be added, but some FH patients do not achieve the target LDL-C with this therapy Therefore, besides these and the most recent but already established therapeutic approaches including PCSK9 inhibitors, inclisiran, and bempedoic acid, new therapies are on the horizon such as gene therapy, CRISPR/Cas9 strategy, etc. This paper focuses on cellular and molecular potential strategies for the treatment of FH.
Keywords: Familial hypercholesterolemia, gene therapy, cellular therapy, autosomal dominant, low-density lipoproteins (LDLs), LDL-receptor.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1871530322666220509040844	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873
Endocrine, Metabolic & Immune Disorders - Drug Targets

Cellular and Molecular Aspects of Managing Familial Hypercholesterolemia: Recent and Emerging Therapeutic Approaches

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