title: Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA.
abstract: Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients.
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ruud S
authors.initials: RS
authors.lastname: Kootte
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Loek P
authors.initials: LP
authors.lastname: Smits
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: van der Valk
authors.affiliation: Cerenis Therapeutics Holding, Toulouse, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dasseux
authors.affiliation: Cerenis Therapeutics Holding, Toulouse, France.
authors.forename: Constance H
authors.initials: CH
authors.lastname: Keyserling
authors.affiliation: Cerenis Therapeutics Holding, Toulouse, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Barbaras
authors.affiliation: Cerenis Therapeutics Holding, Toulouse, France.
authors.forename: John F
authors.initials: JF
authors.lastname: Paolini
authors.affiliation: Heart Institute (Incor), University of Sao Paolo Medical School Hospital, Sao Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-van Thie
authors.affiliation: Radiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: WillemJ M
authors.initials: WM
authors.lastname: Mulder
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: JohnJ P
authors.initials: JP
authors.lastname: Kastelein
authors.affiliation: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.affiliation: Departments of Vascular Medicine and Experimental Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands. Electronic address: e.s.stroes@amc.nl.
authors.forename: ErikS
authors.initials: E
authors.lastname: Stroes
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D052456:Hypoalphalipoproteinemias / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000008:administration & dosage*; D049268:Positron-Emission Tomography; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D016632:Apolipoprotein A-I; C000591544:CER-001; D008076:Cholesterol, HDL; D010743:Phospholipids; D011994:Recombinant Proteins
keywords: apolipoprotein A-I; familial hypoalphalipoproteinemia; reverse cholesterol transport