Gene and cell therapy approaches for familial hypercholesterolemia: An update

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Updated: Aug 16, 2025

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

8.2K

Negin Parsamanesh1, Omid Kooshkaki2, Haleh Siami3

  • 1Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Drug Discovery Today
|December 26, 2022
PubMed

Insights

Familial hypercholesterolemia (FH) is a genetic disorder causing high LDL-C. Gene editing technologies like CRISPR/Cas9 show promise for correcting LDLR gene variations in FH patients, offering new hope for treatment.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cardiovascular Medicine

Background:

  • Familial hypercholesterolemia (FH) is an autosomal codominant disorder increasing risk of early cardiovascular disease due to high LDL-C.
  • Genetic variations in LDLR, APOB, PCSK9, and LIPA are linked to FH.
  • Current therapies are often ineffective for homozygous FH patients, highlighting an unmet need.

Purpose of the Study:

  • To review advanced genetic techniques for correcting FH-causing LDLR gene variations.
  • To explore the potential of gene delivery, gene editing, and stem cell manipulation for FH treatment.
  • To assess the efficacy of CRISPR/Cas9 technology in correcting genetic defects in FH.

Main Methods:

  • Review of in vitro, ex vivo, and in vivo studies utilizing gene editing technologies.
  • Focus on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) systems.
  • Analysis of stem cell manipulation techniques for genetic correction.

Main Results:

  • Gene delivery and editing techniques demonstrate potential for correcting LDLR gene variations in FH models.
  • CRISPR/Cas9 technology has been successfully applied to correct genetic defects causing FH in various study settings.
  • Stem cell manipulation offers another avenue for therapeutic intervention.

Conclusions:

  • Gene editing, particularly CRISPR/Cas9, presents a promising therapeutic strategy for FH.
  • Advanced genetic and stem cell techniques offer potential solutions for patients with severe FH unresponsive to conventional treatments.
  • Further research and development are crucial for translating these findings into clinical applications.

Keywords:
cell therapyfamilial hypercholesterolemiagene therapylow-density lipoprotein receptor

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