Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients...

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Pharmacology

Background:

• Familial hypoalphalipoproteinemia (FHA) is an orphan disease characterized by low HDL cholesterol, impaired cholesterol removal, and increased atherosclerosis risk.
• Reverse cholesterol transport (RCT) mediated by HDL is crucial for preventing atherosclerosis.
• There is a need for effective therapies to improve RCT and reduce cardiovascular burden in FHA patients.

Purpose of the Study:

• To evaluate the efficacy of CER-001, a human apoA-I-containing HDL-mimetic particle, in improving RCT and reducing arterial wall disease in FHA patients.
• To assess the impact of CER-001 on lipid profiles, cholesterol efflux, and fecal sterol excretion.
• To measure changes in carotid artery dimensions and inflammation using advanced imaging techniques.

Main Methods:

• An open-label, uncontrolled proof-of-concept study involving seven FHA patients.
• Subjects received 20 infusions of CER-001 (8 mg/kg) over 6 months.
• Efficacy was assessed through lipoprotein analysis, in vitro cholesterol efflux assays, fecal sterol excretion measurements, and MRI/FDG-PET/CT scans of the carotid artery.

Main Results:

• CER-001 infusions led to significant increases in apoA-I and HDL-cholesterol levels.
• A 44% relative increase in in vitro cellular cholesterol efflux was observed, with a trend towards increased fecal sterol excretion.
• Carotid artery mean vessel wall area and artery wall inflammation (target-to-background ratio) significantly decreased after CER-001 treatment.

Conclusions:

• CER-001 effectively stimulates cholesterol mobilization in FHA patients.
• Treatment with CER-001 reduced artery wall dimension and inflammation, indicating an anti-atherogenic effect.
• These findings support further clinical evaluation of CER-001 for the treatment of FHA.