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.

The HDL mimetic CER-001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency / C. Pavanello, M. Turri, A. Strazzella, P. Tulissi, S. Pizzolitto, G. De Maglio, R. Nappi, L. Calabresi, G. Boscutti. - In: JOURNAL OF INTERNAL MEDICINE. - ISSN 0954-6820. - 291:3(2022), pp. 364-370. [10.1111/joim.13404]

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

C. Pavanello
Primo
;
M. Turri
Secondo
;
A. Strazzella;L. Calabresi
Penultimo
;
2022

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.
CER-001; chronic kidney disease; familial LCAT deficiency; HDL mimetic; lipids
Settore BIO/14 - Farmacologia
Settore MED/14 - Nefrologia
Settore MED/03 - Genetica Medica
Settore MED/09 - Medicina Interna
11-nov-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/884223
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