CER-001 is a recombinant high-density lipoprotein (HDL) mimetic that has orphan drug status.[1] It is in early-stage clinical trials for the potential treatment of hypoalphalipoproteinaemia,[2] acute coronary syndrome (ACS),[3] acute kidney injury (AKI),[4][5][6] atherosclerosis[7] and lecithin cholesterol acyltransferase (LCAT) deficiency.[8] CER-001 is also under investigation as possible agent for treating hyperinflammatory states based on lipid profile alterations due to COVID-19.[9][10]
| Clinical data | |
|---|---|
| Other names | CER-001, CER 001 |
| Routes of administration | Infusion |
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Chemistry edit
CER-001 is an artificially synthesized mimetic of recombinant human apolipoprotein A1 (ApoA1), the main structural protein of natural HDL, together with two phospholipids, which are: sphingomyelin and dipalmitoyl-phosphatidylglycerol.[11]
Mechanism of action edit
CER-001 is designed to mimic the natural structure and function of nascent HDL, also known as pre-beta HDL.[12] This mimicry stimulates cholesterol efflux from macrophages, captures cholesterol and eliminates it via reverse lipid transport (RLT) pathway, also known as reverse cholesterol transport (RCT) pathway.[13]
Clinical trials edit
CER-001 was given in clinical human studies by intravenous infusion.[14] It did not appear to affect clinical chemistry, hematology or coagulation parameters and is considered safe.[14]
References edit
- ^ "EU/3/21/2490 - orphan designation for treatment of lecithin-cholesterol acyltransferase deficiency". European Medicines Agency. Archived from the original on 2022-03-16. Retrieved 2024-03-11.
- ^ "CER-001 for Familial Primary Hypoalphalipoproteinemia". NIHR Innovation Observatory Evidence Briefing. May 2018. Archived from the original on 2024-03-20. Retrieved 2024-03-20.
- ^ Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC, et al. (December 2014). "Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial". European Heart Journal. 35 (46) (published 2024-04-29): 3277–3286. doi:10.1093/eurheartj/ehu171. eISSN 1522-9645. PMC 4258222. PMID 24780501.
- ^ Eckford C (2023-01-17). "CER-001 identified as potential treatment for septic patients". European Pharmaceutical Review. Archived from the original on 2023-01-17. Retrieved 2024-03-09.
- ^ "Abionyx Pharma announces success in fighting sepsis-triggered AKI". european-biotechnology.com. 2023-01-16. Archived from the original on 2023-01-24. Retrieved 2024-03-20.
- ^ Stasi A, Fiorentino M, Franzin R, Staffieri F, Carparelli S, Losapio R, et al. (November 2023). "Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project". BMC Medicine. 21 (1) (published 2023-11-02): 392. doi:10.1186/s12916-023-03057-5. PMC 10621167. PMID 37915050.
- ^ Tardy C, Goffinet M, Boubekeur N, Ackermann R, Sy G, Bluteau A, et al. (January 2014). "CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice". Atherosclerosis. 232 (1) (published 2013-11-08): 110–118. doi:10.1016/j.atherosclerosis.2013.10.018. PMID 24401224.
- ^ Pavanello C, Turri M, Strazzella A, Tulissi P, Pizzolitto S, De Maglio G, et al. (March 2022). "The HDL mimetic CER-001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency". Journal of Internal Medicine. 291 (3) (published 2021-11-11): 364–370. doi:10.1111/joim.13404. PMC 9299003. PMID 34761839.
- ^ Stasi A, Franzin R, Fiorentino M, Squiccimarro E, Castellano G, Gesualdo L (June 2021). "Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications". International Journal of Molecular Sciences. 22 (11): gfac067.086. doi:10.1093/ndt/gfac067.086. PMC 9383927.
- ^ Faguer S, Del Bello A, Danet C, Renaudineau Y, Izopet J, Kamar N (2022-09-26). "Apolipoprotein-A-I for severe COVID-19-induced hyperinflammatory states: A prospective case study". Frontiers in Pharmacology. 13: 936659. doi:10.3389/fphar.2022.936659. PMC 9550000. PMID 36225555.
- ^ "CER-001". Abionyx Pharma SA, Balma, France. Archived from the original on 2020-08-11. Retrieved 2024-04-10.
- ^ Helfand C (2014-01-03). "Cerenis Reports Top-Line Phase II Results for its HDL Mimetic CER-001". Fierce Biotech. Archived from the original on 2020-10-22. Retrieved 2024-03-12.
- ^ Barbaras R (2015-10-06). "Non-clinical development of CER-001". Frontiers in Pharmacology. 6: 220. doi:10.3389/fphar.2015.00220. PMC 4594020. PMID 26500552.
- ^ a b Keyserling CH, Barbaras R, Benghozi R, Dasseux JL (May 2017). "Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings". Clinical Drug Investigation. 37 (5) (published 2017-02-17): 483–491. doi:10.1007/s40261-017-0506-3. PMC 5394142. PMID 28213743.