Persistent Pulmonary Hypertension of the Newborn (PPHN)

Persistent pulmonary hypertension of the newborn (PPHN) is a sustained increase in pulmonary vascular resistance (PVR), stemming from a failure of the circulatory adaptation that is usually made in the minutes following birth. Developing therapy for life-threatening conditions such as PPHN, requires a partner with experience and an end-to-end solutions approach. As a one-stop services provider for drug discovery and development, Protheragen is dedicated to making the transition from bench to bedside a shorter, more efficient process for therapies aimed at deadly diseases with these problems.

Introduction to Persistent Pulmonary Hypertension of the Newborn (PPHN)

Persistent pulmonary hypertension of the newborn (PPHN) is a major cause of morbidity and mortality in the neonate. It is defined by persistent elevation of PVR with failure to increase pulmonary blood flow after birth.

The diseased newborns cannot make their blood oxygenated, resulting in severe respiratory distress, hypoxemia, and finally death. The incidence of PPHN is about 2/1,000 live births and is more common in terms of late preterm neonates.

Fig.1 Pathogenic factors of PPHN. (Singh, Y., and Lakshminrusimha, S., 2021)

Pathogenesis of Persistent Pulmonary Hypertension of the Newborn (PPHN)

There are two core components that likely mediate the pathogenesis of PPHN, both culminating in elevation of PVR at birth: increased pulmonary arteriolar vasoconstrictor effect and vascular structural remodeling, with or without deficient development of the vascular bed. Several perinatal diseases could be incriminated in the occurrence of both these mechanisms and are considered PPHN etiologies. Accordingly, the etiology of PPHN is multifactorial, including multiple perinatal risk factors like maternal exposure risk factors.

Fig.2 Signaling pathways and their interactions are involved in the pathogenesis of PPHN. (Martinho, S., et al., 2020)

Therapeutics Development for Persistent Pulmonary Hypertension of the Newborn (PPHN)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

Through advanced diagnostics, novel therapeutics, and a highly complex disease model development platform, our services cover every side of groundbreaking research. By providing pharmacokinetic testing and extensive preclinical drug safety analysis, each drug is tested for efficacy and proven safe before ascending to the next level. Combining these full-service preclinical capabilities not only provides accelerated solutions, it also increases the probability of success.

Therapeutic Development Services

Animal Model Development for PPHN

Understanding animal models can help to investigate the pathophysiology of PPHN and to evaluate whether potential therapeutic interventions may be effective. Because precise and representative models are fundamental to the success of preclinical experiments, our company provides tailor-made animal model development services according to the demand for PPHN research.

Induced Animal Models

The chemically-induced PPHN model involves the administration of certain chemical agents, to neonatal animals, to induce the pulmonary hypertensive state observed in PPHN.

• U46619-induced model
• L-NAME induced model
• BQ-788 induced model
• Other models

Environmental or Stress-induced Model

The model is induced by prolonged exposure of newborn animals to low oxygen levels, resulting in increased PVR development similar to that of PPHN.

• Hypoxia-induced model
• Other models

Surgical Animal Model

The surgical animal model of PPHN is surgically generated based on the manipulation of neonatal animals to induce an elevation in pulmonary arterial pressure to mimic PPHN.

• Ligated ductus arteriosus model
• Other models

A commitment to excellence and genuine expertise in PPHN and other rare diseases distinguish Protheragen in the cardiovascular field. Partnering with us enables access to leading-edge technology and decades of experience. Learn how our customized programs can accelerate your research, and connect with us today to determine how we can make an impact on rare cardiovascular disease therapy development.

References

• Martinho, Sofia et al. "Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches." Frontiers in pediatrics 8 (2020): 342.
• Singh, Yogen, and Satyan Lakshminrusimha. "Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn." Clinics in perinatology 48.3 (2021): 595-618.