CER-001

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CER-001
Clinical data
Other namesCER-001, CER 001
Routes of
administration 		Infusion
Identifiers
CAS Number
DrugBank

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]

Contents

Chemistry

CER-001 is an artificially synthesized mimetic of recombinant human apolipoprotein AI (ApoA1), the main structural protein of natural HDL, together with two phospholipids, which are: sphingomyelin and dipalmitoyl-phosphatidylglycerol. [11]

Mechanism of action

Mechanism of action of CER-001 CER-001 mechanism of action.jpg
Mechanism of action of CER-001

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]

Pre-clinical studies

A pre-clinical study in mice investigated whether LCAT deficiency affects the catabolic behavior of CER-001 and evaluated the effects of the substance on kidney diseases associated with LCAT deficiency. In the mouse model, it appeared to improve the dyslipidemia typically associated with LCAT deficiency and mitigate renal damages in LCAT deficiency. [14]

Clinical trials

CER-001 was given in clinical human studies by intravenous infusion. [15] It did not appear to affect clinical chemistry, hematology or coagulation parameters and is considered safe. [15]

References

  1. ↑ "EU/3/21/2490 - orphan designation for treatment of lecithin-cholesterol acyltransferase deficiency". European Medicines Agency. 30 September 2021. Archived from the original on 2022-03-16. Retrieved 2024-03-11.
  2. ↑ "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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ "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.
  6. ↑ 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) 392 (published 2023-11-02). doi: 10.1186/s12916-023-03057-5 . PMC   10621167 . PMID   37915050.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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 .
  10. ↑ 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.
  11. ↑ "CER-001". Abionyx Pharma SA, Balma, France. Archived from the original on 2020-08-11. Retrieved 2024-04-10.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Ossoli A, Strazzella A, Rottoli D, Zanchi C, Locatelli M, Zoja C, et al. (2020-12-09). "CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency". Metabolism: Clinical and Experimental. 116 154464. doi:10.1016/j.metabol.2020.154464. PMID   33309714.
  15. 1 2 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.
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