SIALIDASE INHIBITION AS ANTIATHEROSCLEROTIC THERAPY

Summary

The aim of this double-blind, randomized, placebo-controlled, multicenter study is to evaluate the pathogenetic effects of the dietary supplement "Tertinat" on a fundamental mechanism of atherosclerosis development: its ability to inhibit pathological desialylation of low-density lipoproteins (LDL). According to the protocol's scientific hypothesis, the loss of sialic acid from the surface of LDL converts them into highly atherogenic particles, which are actively captured by vascular macrophages, triggering the formation of unstable atherosclerotic plaques. Over 24 months of daily administration of 330 mg of epigallocatechin-3-gallate, along with standard therapy, will evaluate not only the incidence of major cardiovascular events (MACE) in atherosclerotic patients who have undergone the procedure of surgical revascularization, but also the direct dynamics of recovery of sialic acid levels in LDL particles in patients' blood. The study aims to confirm that preventing LDL desialylation reduces overall serum atherogenicity, prevents cholesterol accumulation within macrophages in vivo, and thereby provides a proven clinical effect - a reduced risk of myocardial infarction, stroke, unstable angina, heart failure, and the need for repeated revascularization in patients after coronary artery bypass grafting or stenting.

Timeline

Start

2024-08-29

Primary completion

2027-07-15

Completion

2027-08-31

Publications

• Background Mezentsev A, Bezsonov E, Kashirskikh D, Baig MS, Eid AH, Orekhov A. Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside. Biomedicines. 2021 May 25;9(6):600. doi: 10.3390/biomedicines9060600.
• Background Liu Y, Zhang H, Dai X, Zhu R, Chen B, Xia B, Ye Z, Zhao D, Gao S, Orekhov AN, Zhang D, Wang L, Guo S. A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng. Phytomedicine. 2021 Nov;92:153717. doi: 10.1016/j.phymed.2021.153717. Epub 2021 Sep 10.
• Background Simental-Mendia LE, Shah N, Sathyapalan T, Majeed M, Orekhov AN, Jamialahmadi T, Sahebkar A. Effect of Curcumin on Glycaemic and Lipid Parameters in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Reprod Sci. 2022 Nov;29(11):3124-3133. doi: 10.1007/s43032-021-00761-6. Epub 2021 Oct 15.
• Background P Karagodin V, I Summerhill V, Yet SF, Orekhov AN. The Anti-atherosclerotic Effects of Natural Polysaccharides: From Phenomena to the Main Mechanisms of Action. Curr Pharm Des. 2022;28(22):1823-1832. doi: 10.2174/1381612828666220518095025.
• Background Glanz V, Bezsonov EE, Soldatov V, Orekhov AN. Thirty-Five-Year History of Desialylated Lipoproteins Discovered by Vladimir Tertov. Biomedicines. 2022 May 19;10(5):1174. doi: 10.3390/biomedicines10051174.
• Background Markina YV, Kirichenko TV, Markin AM, Yudina IY, Starodubova AV, Sobenin IA, Orekhov AN. Atheroprotective Effects of Glycyrrhiza glabra L. Molecules. 2022 Jul 22;27(15):4697. doi: 10.3390/molecules27154697.
• Background Hassanizadeh S, Shojaei M, Bagherniya M, Orekhov AN, Sahebkar A. Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials. Biofactors. 2023 May-Jun;49(3):512-533. doi: 10.1002/biof.1932. Epub 2023 Jan 6.
• Background Dabravolski SA, Sukhorukov VN, Melnichenko AA, Khotina VA, Orekhov AN. Oligosaccharides as Potential Therapeutics against Atherosclerosis. Molecules. 2023 Jul 17;28(14):5452. doi: 10.3390/molecules28145452.
• Background Dabravolski SA, Sukhorukov VN, Melnichenko AA, Khotina VA, Orekhov AN. Potential Application of the Plant-Derived Essential Oils for Atherosclerosis Treatment: Molecular Mechanisms and Therapeutic Potential. Molecules. 2023 Jul 26;28(15):5673. doi: 10.3390/molecules28155673.
• Background Poznyak AV, Kashirskikh DA, Postnov AY, Popov MA, Sukhorukov VN, Orekhov AN. Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis. Braz J Med Biol Res. 2023 Dec 11;56:e12972. doi: 10.1590/1414-431X2023e12972. eCollection 2023.
• Background Orekhov A, Sukhorukov V, Melnichenko A. Is Oxidized Low-Density Lipoprotein a Principal Actor in Atherogenesis? Curr Med Chem. 2024;31(42):6909-6910. doi: 10.2174/0109298673283640231208103306. No abstract available.
• Background Orekhov A, Khotina V, Sukhorukov V, Sobenin I. Non-oxidative vs Oxidative Forms of Modified Low-density Lipoprotein: What is More Important in Atherogenesis? Curr Med Chem. 2024;31(17):2309-2313. doi: 10.2174/0109298673294245240102105814. No abstract available.
• Background Orekhov AN. We Must Abandon the Myth: Oxidized Low-density Lipoprotein is not a Lipoprotein that Plays a Key Role in Atherogenesis. Curr Med Chem. 2025;32(15):2899-2914. doi: 10.2174/0109298673301236240311113807.
• Background Poznyak AV, Yakovlev AA, Popov Mcapital A, Cyrillic, Zhuravlev AD, Sukhorukov VN, Orekhov AN. WITHDRAWN: Coronary atherosclerotic plaque regression strategies. J Biomed Res. 2024 May 29:1-21. doi: 10.7555/JBR.37.20230223. Online ahead of print.
• Background Kashirskikh D, Chicherina N, Glanz V, Orekhov A, Sobenin I. Mouse Model of Low-density Lipoprotein Desialylation In Vivo. Curr Med Chem. 2026;33(8):1523-1537. doi: 10.2174/0109298673294745240528092506.

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Indications