The HDL mimetic CER-001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency.

Abstract

BACKGROUND:

Kidney failure is the major cause of morbidity and mortality in familial lecithin:cholesterol acyltransferase deficiency (FLD), a rare inherited lipid disorder with no cure. Lipoprotein X (LpX), an abnormal lipoprotein, is primarily accountable for nephrotoxicity.

METHODS:

CER-001 was tested in an FLD patient with dramatic kidney disease for 12 weeks.

RESULTS:

Infusions of CER-001 normalized the lipoprotein profile, with a disappearance of the abnormal LpX in favour of normal-sized LDL. The worsening of kidney function was slowed by the treatment, and kidney biopsy showed a slight reduction of lipid deposits and a stabilization of the disease. In vitro experiments demonstrate that CER-001 progressively reverts lipid accumulation in podocytes by a dual effect: remodelling plasma lipoproteins and removing LpX-induced lipid deposit.

CONCLUSION:

This study demonstrates that CER-001 may represent a therapeutic option in FLD patients. It also has the potential to be beneficial in other renal diseases characterized by kidney lipid deposits.

• Authors: Chiara Pavanello, Marta Turri, Arianna Strazzella, Patrizia Tulissi, Stefano Pizzolitto, Giovanna De Maglio, Riccardo Nappi, Laura Calabresi, Giuliano Boscutti
• Journal: Journal of internal medicine (J Intern Med) Vol. 291 Issue 3 Pg. 364-370 (03 2022) ISSN: 1365-2796 [Electronic] England
• PMID: 34761839 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Chemical References

• Apolipoprotein A-I
• CER-001
• Lipoproteins
• Phospholipids
• Recombinant Proteins
• Phosphatidylcholine-Sterol O-Acyltransferase

Topics

• Apolipoprotein A-I (therapeutic use)
• Humans
• Kidney (pathology)
• Lecithin Cholesterol Acyltransferase Deficiency (drug therapy, pathology)
• Lipoproteins
• Phosphatidylcholine-Sterol O-Acyltransferase (pharmacology, therapeutic use)
• Phospholipids
• Recombinant Proteins