Chemistry:CER-001
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]
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
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
- ↑ "EU/3/21/2490 - orphan designation for treatment of lecithin-cholesterol acyltransferase deficiency". European Medicines Agency. 30 September 2021. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-21-2490.
- ↑ "CER-001 for Familial Primary Hypoalphalipoproteinemia" (in en-US). NIHR Innovation Observatory Evidence Briefing. May 2018. https://www.io.nihr.ac.uk/techbriefings/cer-001-for-familial-primary-hypoalphalipoproteinemia/.
- ↑ "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): 3277–3286. December 2014. 2024-04-29. doi:10.1093/eurheartj/ehu171. PMID 24780501.
- ↑ "CER-001 identified as potential treatment for septic patients" (in en). 2023-01-17. https://www.europeanpharmaceuticalreview.com/news/178595/cer-001-potential-treatment-identified-for-septic-patients/.
- ↑ "Abionyx Pharma announces success in fighting sepsis-triggered AKI" (in en). 2023-01-16. https://european-biotechnology.com/up-to-date/latest-news/news/abionyx-pharma-announces-success-in-fighting-sepsis-triggered-aki.html.
- ↑ "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). November 2023. 2023-11-02. doi:10.1186/s12916-023-03057-5. PMID 37915050.
- ↑ "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): 110–118. January 2014. 2013-11-08. doi:10.1016/j.atherosclerosis.2013.10.018. PMID 24401224.
- ↑ "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): 364–370. March 2022. 2021-11-11. doi:10.1111/joim.13404. PMID 34761839.
- ↑ "Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications". International Journal of Molecular Sciences 22 (11). June 2021. doi:10.1093/ndt/gfac067.086.
- ↑ "Apolipoprotein-A-I for severe COVID-19-induced hyperinflammatory states: A prospective case study". Frontiers in Pharmacology 13. 2022-09-26. doi:10.3389/fphar.2022.936659. PMID 36225555.
- ↑ "CER-001". Abionyx Pharma SA, Balma, France. https://www.abionyx.com/en/our-assets/cer-001.
- ↑ "Cerenis Reports Top-Line Phase II Results for its HDL Mimetic CER-001". 2014-01-03. https://www.fiercebiotech.com/biotech/cerenis-reports-top-line-phase-ii-results-for-its-hdl-mimetic-cer-001.
- ↑ "Non-clinical development of CER-001". Frontiers in Pharmacology 6: 220. 2015-10-06. doi:10.3389/fphar.2015.00220. PMID 26500552.
- ↑ "CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency". Metabolism: Clinical and Experimental 116. 2020-12-09. doi:10.1016/j.metabol.2020.154464. PMID 33309714.
- ↑ 15.0 15.1 "Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings". Clinical Drug Investigation 37 (5): 483–491. May 2017. 2017-02-17. doi:10.1007/s40261-017-0506-3. PMID 28213743.
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