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Updated: Jul 8, 2026
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
Genetics of cholesterol and lipoprotein metabolism
1Centre de Recherche du CHUM, Université de Montréal, Hôpital Notre-Dame, 1560, rue Sherbrooke Est, Local M-5226, Montréal, QC H2L 4M1, Canada. mark.e.samuels@umontreal.ca
Abstract:
The goal of drugs is to modulate the activity of particular gene products in order to change the physiological state of an organism from disease to health. Because of the complexity of development and metabolism, it is difficult to extrapolate from in vitro experimental results using purified reagents, to predict the actual change in behavior of an entire biological system in vivo. Metabolic control analysis provides a theoretical framework for understanding the basis of this apparent paradox. In practice, genetics provides a unique opportunity to observe the behavior of whole systems in the presence of different amounts of a particular gene product, resulting from varying genomic sequences of alleles governing the expression or activity of that gene product. This is most evident in the case of monogenic disorders, in which severe mutations in a gene lead to clear effects on gene product activity, and strong causal genotype/phenotype correlations can be inferred. Among the many therapeutic targets currently in development for treatment of dyslipidemia, a major risk factor for cardiovascular disease, there is particular interest in those targets whose coding genes are associated with molecularly characterized monogenic human conditions. Herein a selection of these genetic disorders, especially those involving HDL and LDL cholesterol, is discussed in the context of ongoing or potential therapeutic development programs. This article also includes recent patent review coverage.
Insights
Genetics reveals how gene variations impact health, offering insights into treating diseases like dyslipidemia. Studying monogenic disorders aids in developing targeted therapies for cardiovascular disease risk factors.
Area of Science:
- Biochemistry and Genetics
- Pharmacology
- Systems Biology
Background:
- Drug development faces challenges extrapolating in vitro findings to complex in vivo biological systems.
- Metabolic control analysis offers a framework to understand system-level biological responses.
- Genetics, particularly monogenic disorders, provides a powerful model for observing gene product effects on whole systems.
Purpose of the Study:
- To explore the therapeutic potential of targeting genes associated with monogenic disorders for dyslipidemia treatment.
- To review genetic conditions impacting HDL and LDL cholesterol levels.
- To connect genetic insights with ongoing and potential drug development programs.
Main Methods:
- Analysis of monogenic human conditions with clear genotype/phenotype correlations.
- Review of therapeutic targets for dyslipidemia linked to specific genes.
- Examination of recent patent literature relevant to genetic therapies for lipid disorders.
Main Results:
- Monogenic disorders provide direct evidence of gene product activity influencing physiological states.
- Several genetic conditions related to HDL and LDL cholesterol are identified as promising therapeutic targets.
- Ongoing research and patent filings indicate active development in genetically informed dyslipidemia treatments.
Conclusions:
- Understanding monogenic disorders is crucial for developing effective treatments for complex diseases like dyslipidemia.
- Targeting genes implicated in monogenic lipid disorders offers a promising strategy for cardiovascular disease prevention.
- Genetic insights are driving innovation in therapeutic development for dyslipidemia and related conditions.
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