RESUMO
Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down sFLT1 expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.
Assuntos
Terapia Genética , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/terapia , Terapia Genética/métodos , Receptor 1 de Fatores de Crescimento do Endotélio VascularRESUMO
La terapia anti-retroviral utilizada durante el embarazo en madres infectadas con VIH disminuye la transmisión perinatal del virus. Esto es válido para mono, bi y tri-terapia (HAART), siendo mayor el efecto de esta última. Sin embargo, cuando se utilizan dichas terapias se debe tener en consideración riesgos potenciales para la madre e hijo (hiperglicemia, acidosis láctica, toxicidad mitocondrial, rash cutáneo, daño hepático, síndrome hipertensivo y parto prematuro). La operación cesárea electiva reduce la transmisión perinatal del virus en pacientes sin terapia o monoterapia. Con tri-terapia este beneficio no está demostrado. Este artículo revisa la evidencia de efectos benéficos y adversos de la terapia anti-retroviral y de la operación cesárea y propone una pauta de manejo de las pacientes infectadas con VIH en el embarazo.