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5th Edition of Cardiology World Conference

September 5-7, 2024 | Madrid, Spain

September 05 -07, 2024 | Madrid, Spain
Cardio 2024

Thomas Bernd Dschietzig

Thomas Bernd Dschietzig, Speaker at Cardiovascular Conference
Relaxera GmbH & Co. KG, Germany
Title : The development of human relaxin-2 for Heart Failure with preserved Ejection Fraction, HFpEF

Abstract:

Human relaxin-2 (hRlx-2) is a hormone of pregnancy that has engendered a great deal of interest as a therapy for various cardiovascular and inflammatory diseases, among them Acute Heart Failure and Systemic Scleroderma. Here, we propose and summarize data showing that Rlx-2 represents a strong drug candidate for the treatment of HFpEF, a hitherto unmet medical need, and outline the upcoming pharmacological development.

In particular, the talk summarizes data obtained in the rat ZSF1 HFpEF model. ZSF1 rats (9-weeks old, either sex) were placed on a high fat diet for 11 weeks and serial echocardiograms were used to track the development and severity of diastolic dysfunction (DD). Once severe HFpEF was established rats received daily sc. injections of hRlx-2 (100µg/kg) or vehicle. After 2 weeks, hearts were perfused with a voltage-sensitive dye (RH237) and a Ca2+ indicator (Rhod-2/AM) to optically map action potentials and Ca2+ transients to analyze the arrhythmia phenotype. Tissue sections for immunofluorescence and Westerns were used to measure changes in fibrosis (collagen 1), Nav1.5, connexin 43, Wnt1 and β-catenin. Rlx-2 suppressed atrial and ventricular arrythmia and significantly increased Cx43 expression, Nav1.5 and β-catenin at intercalated disks. It reduced collagen deposition back to normal levels and increased myocardial Wnt1 expression. In summary, the ZSF1 diabetic rat on a high-fat diet recapitulates human HFpEF with lung edema, fibrosis, and DD as well as atrial and ventricular arrhythmias. Rlx-2 injections reversed DD, left atrial enlargement, and fibrosis. Rlx-2 also abolished the pro-arrhythmic phenotype by increasing conduction velocity, Cx43, and Nav1.5. Thus, daily subQ hRlx-2 injections were highly effective as a therapy for HFpEF. The peptide is being developed for clinical trials in HFpEF.

Biography:

Thomas Bernd Dschietzig studied Medicine at Charité, the Medical Faculty of the Humboldt University of Berlin, Germany, and is a specialist of Internal Medicine focused on cardiovascular research. His lab and clinical work has been focused on the study of physiology and pathophysiology of the naturally occurring peptide hormone human relaxin-2. He is Chief Executive Officer and co-founder of Relaxera, a pharma company dedicated to develop synthetic human relaxin-2 for chronic clinical use in cardio-vascular disease, especially in Heart Failure with Preserved Ejection Fraction, HFpEF.

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