Основні поняття
An investigational monoclonal agonist antibody REGN5381 targets the membrane-bound guanylate cyclase receptor NPR1 to induce active-like receptor conformation, resulting in hemodynamic effects that preferentially lower venous pressures to treat heart failure.
Анотація
The content discusses the development of an investigational monoclonal agonist antibody called REGN5381 that targets the NPR1 receptor. NPR1 is the receptor for natriuretic peptides, which are counter-regulatory hormones released in heart failure to induce vasodilation, diuresis, and natriuresis, thereby lowering venous pressures and relieving venous congestion.
The key highlights are:
- Genetic analysis of over 700,000 individuals showed that lifelong exposure to coding variants of the NPR1 gene is associated with changes in blood pressure and risk of heart failure.
- REGN5381 is an allosteric agonist of NPR1 that induces an active-like receptor conformation, leading to hemodynamic effects that preferentially target the venous vasculature.
- In animal models, REGN5381 reduced systolic blood pressure and venous pressure without obvious changes in diuresis and natriuresis.
- In healthy human volunteers, REGN5381 produced the expected hemodynamic effects reflecting reductions in venous pressures, without obvious changes in diuresis and natriuresis.
- These data support the development of REGN5381 for long-lasting and selective lowering of venous pressures that drive symptomatology in patients with heart failure.
Статистика
Heart failure is a leading cause of morbidity and mortality.
Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides.
Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect.
Цитати
"Here we report that in a human genetic analysis of over 700,000 individuals, lifelong exposure to coding variants of the NPR1 gene is associated with changes in blood pressure and risk of heart failure."
"REGN5381, an allosteric agonist of NPR1, induces an active-like receptor conformation that results in haemodynamic effects preferentially on venous vasculature, including reductions in systolic blood pressure and venous pressure in animal models."
"In healthy human volunteers, REGN5381 produced the expected haemodynamic effects, reflecting reductions in venous pressures, without obvious changes in diuresis and natriuresis."