Lomitapide modifies high-density lipoprotein function in homozygous familial hypercholesterolaemia

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Pharmacology

Background:

• Lomitapide is an approved treatment for homozygous familial hypercholesterolemia (HoFH).
• It effectively reduces plasma low-density lipoprotein cholesterol (LDL-C).
• This study investigates lomitapide's impact on HDL and cholesterol efflux in HoFH patients.

Purpose of the Study:

• To evaluate the effect of lomitapide on HDL cholesterol (HDL-C) levels.
• To assess changes in cholesterol efflux capacity (CEC) pathways.
• To understand lomitapide's role in reverse cholesterol transport in HoFH.

Main Methods:

• Analysis of plasma samples from 17 HoFH patients in a phase 3 clinical study.
• Measurement of HDL-C levels at baseline and during lomitapide treatment.
• Assessment of CEC via ABCA1, ABCG1, and SR-BI pathways.

Main Results:

• Lomitapide significantly decreased LDL-C and apo B levels (p < 0.01).
• HDL-C showed a small increase (4.2%) with high-dose lomitapide, while apo A-I decreased slightly (3%).
• Total efflux and ABCA1-mediated CEC decreased, with a dose-dependent increase in SR-BI cholesterol uptake.

Conclusions:

• Lomitapide may promote HDL particle lipidation independently of ABCA1 and ABCG1.
• The SR-BI pathway appears to be involved in this process.
• Lomitapide's effect on reverse cholesterol transport in HoFH patients may be mediated through SR-BI receptors.