Driving innovations in a field of diagnostics & treatment of chronic kidney disease, vascular disease & preeclampsia.
Driving innovations in a field of diagnostics & treatment of chronic kidney disease, vascular disease & preeclampsia.
Driving innovations in a field of diagnostics & treatment of chronic kidney disease, vascular disease & preeclampsia.
Driving innovations in a field of diagnostics & treatment of chronic kidney disease, vascular disease & preeclampsia.
Challenge
Approximately 850 million people worldwide are estimated to have kidney disease. As many as 9 out of 10 individuals with chronic kidney disease (CKD) are unaware that they have this condition.
Salt consumption, ageing and population growth especially in 3rd countries will translate to large increases in the prevalence of CKD in the coming decades. CKD is the third fastest-growing cause of death globally. By 2040, chronic kidney disease is projected to be the 5th highest cause of years of life lost globally (source: Nature Reviews Nephrology).
There is no cure for chronic kidney disease although current treatment can slow the progression of the disease if diagnosed early. But once RRT is commenced, the patient’s life expectancy is expected to be 5 to 10 years unless a kidney transplant is obtained.
The product
Based on many years of experience and research, Padakonn Pharma OÜ has developed 4 clones of antibodies which block fibrosis and reduce blood pressure in chronic kidney disease
- monoclonal and do not lead to unpredictable cross-immunoreactivity;
- have no contraindications to the amount of use;
- prevent developing of the hard cases of CKD and increase the patient's chances to a transplant;
- prevent developing of cardiorenal syndrome, vascular diseases, fibrosis, hard cases of preeclampsia;
- work rapid and safe extracorporeal even without RRT;
- based on standard HiTrap NHS-Activated filters which are compatible with any dialysis machine;
Antibody-bounded HiTrap NHS-Activated filters, developed by Padakonn, block Marinobufagenin in the blood circulation of patients in order to prevent progression of fibrosis, kidney & vascular diseases, preeclampsia.
Mission
Improve the quality and duration of life of patients with Chronic Kidney Disease, Preeclampsia & Cardiovascular morbidity, reducing the burden on the healthcare system.
Mission
Improve the quality and duration of life of patients with Chronic Kidney Disease, Preeclampsia & Cardiovascular morbidity, reducing the burden on the healthcare system.
Science
Role of sodium potassium pump
Role of Marinobufagenin
Preeclampsia too
Another example of the harmful effects of MBG is Preeclampsia (PE), which keeps number 1 in the list of pregnancy-induced reasons for fetal & maternal mortality (up to 5%) & morbidity. Elevated plasma levels of cardiotonic steroids (CTS) were detected in patients with PE more than 20 years ago [3]. In advanced stages of PE levels of MBG are dramatically increased, indicating that CKD & PE have similar pathogenesis & blocking MBG represents an important target for a novel therapy [4,5].
Not only stops, but also reverses
The Team
Alexei Bagrov, MD, PhD
Principal Investigator
Co-founder
Israel / Estonia / USA
David Adair, MD, MBA
Managing Partner
Olle Melander, MD, PhD
Research & Development
Mai Rosenberg, MD, PhD
Chief Clinical
Kirill Smirnov, MBA
Chief Business Officer
CEO
References:
[1] “Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets”. Pharmacol Rev. 2009 Mar;61(1):9-38. doi: 10.1124/pr.108.000711. PMID: 19325075; PMCID: PMC2763610.
[2] “Endogenous cardiotonic steroids in chronic renal failure”. Nephrol Dial Transplant. 2011 Sep;26(9):2912-9. doi: 10.1093/ndt/gfq772. Epub 2011 Feb 3. PMID: 21292813; PMCID: PMC3203407.
[3] “Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia”. Int J Mol Sci. 2018 Aug 13;19(8):2377. doi: 10.3390/ijms19082377. PMID: 30104471; PMCID: PMC6121256.
[4] “Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists”. J Hypertens. 2015 Aug;33(8):1602-10. doi: 10.1097/HJH.0000000000000591. PMID: 26136067; PMCID: PMC4547457.
[5] “Acute salt loading and cardiotonic steroids in resistant hypertension”. Curr Top Membr. 2019;83:1-13. doi: 10.1016/bs.ctm.2019.01.005. Epub 2019 Feb 18. PMID: 31196601; PMCID: PMC7508670.
[6] “Silencing of Fli1 Gene Mimics Effects of Preeclampsia and Induces Collagen Synthesis in Human Umbilical Arteries”. Am J Hypertens. 2022 Sep 1;35(9):828-832. doi: 10.1093/ajh/hpac065. PMID: 35569064.
[7] “Canrenone Restores Vasorelaxation Impaired by Marinobufagenin in Human Preeclampsia”. Int J Mol Sci. 2022 Mar 19;23(6):3336. doi: 10.3390/ijms23063336. PMID: 35328757.
[8] “Silencing of PKG1 gene sensitizes vascular smooth muscle cells to pro-fibrotic effect of marinobufagenin and mimics effect of aging”. Fedorova OV, Shilova VY, Marshall CA, Zernetkina V, Lakatta EG, Bagrov AY. J Am Heart Assoc 2023 Jun 20;12(12):e028768. doi: 10.1161/JAHA.122.028768. PMID: 37301747
[9] “Endogenous bufadienolides, aldosterone antagonists and fibrosis in chronic kidney disease”. Frontiers in Pharmacology: https://doi.org/10.3389/fphar.2024.1431216
[10] “Antibody against Na/K-ATPase Inhibitor Lowers Blood Pressure and Increases Vascular Fli1 in Experimental Preeclampsia”. Am J Hypertens. 2020 May 21;33(6):514-519. doi: 10.1093/ajh/hpz180. PMID: 31713584; PMCID: PMC7241934;
[11] “High salt is a risk factor for cardiovascular and kidney diseases. What is next, fibrosis?” J Hypertens. 2021 Jul 1;39(7):1309-1310. doi: 10.1097/HJH.0000000000002853. PMID: 34074968;
[12] “Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated” by CYP27A1 via Bile Acid Pathway. Circ Cardiovasc Genet. 2015 Oct;8(5):736-45. doi: 10.1161/CIRCGENETICS.115.001217. Epub 2015 Sep 15. PMID: 26374826; PMCID: PMC4618091.
[13] “Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options“ Jankowski J, Floege J, Fliser D, Böhm M, Marx N. Circulation. 2021 Mar 16;143(11):1157-1172. doi: 10.1161/CIRCULATIONAHA.120.050686. Epub 2021 Mar 15. PMID: 33720773; PMCID: PMC7969169.
[14] “Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia.” Fedorova OV, Ishkaraeva VV, Grigorova YN, Reznik VA, Kolodkin NI, Zazerskaya IE, Zernetkina Z, Agalakova NI, Tapilskaya NI, Adair CD, Lakatta EG, Bagrov AY. Int J Mol Sci. 2018 Aug 13;19(8). pii: E2377. doi: 10.3390/ijms19082377.