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El anticuerpo agonista del receptor de la guanylata ciclasa NPR1 regula el tono vascular
Michael E Dunn1, Aaron Kithcart2, Jee Hae Kim2
1Regeneron Pharmaceuticals, Tarrytown, NY, USA. michael.dunn@regeneron.com.
Nature
|September 11, 2024
Resumen
Las variantes genéticas en el gen del receptor del péptido natriurético 1 (NPR1) influyen en el riesgo de insuficiencia cardíaca. Un nuevo anticuerpo, REGN5381, reduce selectivamente la presión venosa, ofreciendo un nuevo tratamiento potencial para pacientes con insuficiencia cardíaca.
Área de la Ciencia:
- Medicina cardiovascular
- Farmacología
- La genética
Sus antecedentes:
- La insuficiencia cardíaca es una de las principales causas de enfermedad y muerte.
- Los péptidos natriuréticos y su receptor (NPR1) juegan un papel en la regulación de la presión arterial y el equilibrio de líquidos.
- Los tratamientos existentes que utilizan péptidos natriuréticos tienen limitaciones debido a la corta duración de su efecto.
Objetivo del estudio:
- Investigar la asociación entre las variantes genéticas del gen NPR1 y el riesgo de insuficiencia cardíaca.
- Desarrollar y evaluar un nuevo agente terapéutico dirigido al receptor NPR1 para el tratamiento de la insuficiencia cardíaca.
Principales métodos:
- El análisis genético humano de más de 700.000 individuos.
- Desarrollo de REGN5381, un anticuerpo agonista monoclonal dirigido al receptor NPR1.
- Evaluación de los efectos hemodinámicos de REGN5381 en modelos animales y en voluntarios humanos sanos.
Principales resultados:
- La exposición de por vida a las variantes del gen NPR1 está relacionada con la alteración de la presión arterial y el riesgo de insuficiencia cardíaca.
- REGN5381 demostró una reducción preferente de la presión venosa y la presión arterial sistólica en modelos animales.
- En humanos, REGN5381 indujo los efectos hemodinámicos esperados, reduciendo la presión venosa sin cambios significativos en la diuresis o la natriuresis.
Conclusiones:
- Los conocimientos genéticos sobre la función de NPR1 proporcionan una base para nuevas terapias de insuficiencia cardíaca.
- REGN5381 es prometedor como agente terapéutico de larga duración para reducir selectivamente la presión venosa en la insuficiencia cardíaca.
- Se apoya el desarrollo de REGN5381 para el tratamiento de los síntomas de insuficiencia cardíaca provocados por elevadas presiones venosas.
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