Treatment of homozygous familial hypercholesterolaemia
File(s)
Published version
Author(s)
Cegla, Jaimini
Walji, Shahenaz
Barton, Lucy
Neuwirth, Claire
Thompson, Gilbert
Type
Journal Article
Abstract
Homozygous familial hypercholesterolemia is a rare, life-threatening, genetic disorder characterized by severe hypercholesterolemia, xanthomata, and accelerated atherosclerosis. Untreated, it results in aortic root and coronary artery disease in childhood or adolescence. The introduction of plasma exchange 50 years ago marked a novel therapeutic approach to reducing low-density lipoprotein in these patients and eventually resulted in resolution of tendon xanthomas, arrested progression of atherosclerosis, and increased longevity. Here the authors describe the transition from unselective plasma exchange to the various forms of selective lipoprotein apheresis now in use and consider the remarkable developments in lipid-lowering pharmacotherapy in the current poststatin era. These include small molecules inhibiting microsomal triglyceride transfer protein, monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 and angiopoietin-like-3, and gene-directed therapies such as short interfering RNA. Finally, clustered regularly interspaced short palindromic repeats-mediated gene editing holds great promise as a one-off treatment, with the potential to permanently lower low-density lipoprotein cholesterol in both heterozygous and homozygous patients with familial hypercholesterolemia.
Date Issued
2025-05-01
Date Acceptance
2025-03-10
Citation
JACC: Advances, 2025, 4 (5)
ISSN
2772-963X
Publisher
Elsevier
Journal / Book Title
JACC: Advances
Volume
4
Issue
5
Copyright Statement
© 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Identifier
10.1016/j.jacadv.2025.101708
Publication Status
Published
Article Number
ARTN 101708
Date Publish Online
2025-04-26