Title:Cellular and Molecular Aspects of Managing Familial Hypercholesterolemia: Recent and Emerging Therapeutic Approaches
Volume: 22
Issue: 10
Author(s): Forough Taheri, Eskandar Taghizadeh, Fatemeh Baniamerian, Daryoush Rostami, Ahmad Rozeian, Seyed Mohammad Gheibi hayat, Tannaz Jamialahmadi, Željko Reiner and Amirhossein Sahebkar*
Affiliation:
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Familial hypercholesterolemia, gene therapy, cellular therapy, autosomal dominant, low-density lipoproteins (LDLs), LDL-receptor.
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.
