Clinical InvestigationValvular and Congenital Heart DiseaseThe effect of an apolipoprotein A-I–containing high-density lipoprotein–mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study
Section snippets
Methods
This phase 2 study (clinical trial register NCT01412034) was conducted in accordance with the Declaration of Helsinki and in compliance with current Good Clinical Practice. The multicenter study was designed by the sponsor (Cerenis Therapeutics Holding, Toulouse, France) in collaboration with the academic investigators. The protocol was approved by the local institutional review boards, and all participants provided written informed consent. This study was funded by a research grant from
Baseline characteristics
Baseline characteristics are listed in Table I. Twenty-three patients were included, of whom 11 were homozygous carriers of LDLR mutations, 3 were homozygous carriers of apoB mutations, 6 were compound heterozygous carriers of LDLR mutations, and 3 were double heterozygous carriers of LDLR and apoB mutations. The mean age was 39.4 years ± 13.4 years, and baseline lipid profiles showed a mean LDL-C level of 214.2 ± 81.5 mg/dL and an HDL-C level of 42.6 ± 11.6 mg/dL. All 23 patients were using
Main findings
In the current trial, we found that plasma apoA-I levels transiently increased significantly in patients with HoFH after infusion therapy with CER-001, an HDL-mimetic particle. We observed a beneficial effect on MVWA, the primary efficacy outcome, and a concomitant trend toward a reduction in MVWT after treatment with 12 infusions of CER-001 during a 24-week period. Infusions with CER-001 were generally well tolerated. These data imply that CER-001 infusions may reverse atherogenic artery wall
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2021, Nutrition, Metabolism and Cardiovascular DiseasesSynthetic high-density lipoproteins delivering liver X receptor agonist prevent atherogenesis by enhancing reverse cholesterol transport
2021, Journal of Controlled ReleaseCitation Excerpt :Only 2–5% of all endogenous HDL are classified as pre-β based on its electrophoretic mobility and discoidal shape [22]. Clinically tested synthetic pre-β HDL products consist of lipid bilayers wrapped around by either full-length apolipoprotein A-I (apoA-I) [23–25] or apoA-I synthetic peptide (ETC-642) [26] to form nanodisc structures with diameters of 8–12 nm. Due to their small size, pre-β HDL are capable of accumulating in the atheroma area where they efflux the excess of cholesterol from cholesterol-laden macrophages and, subsequently, deliver to the liver for elimination [7,22].
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Both authors contributed equally.