Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension that comprises the pathological remodeling of pulmonary arteries leading to right ventricular failure and death. Protheragen is a leading research service provider transforming the way rare cardiovascular diseases like PAH are treated. We provide full drug discovery and development services from diagnostics and therapeutics to diseases model generation.
Introduction to Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a rare, but progressive disease affecting adults with remodeling of the pulmonary arteries and vasculature. The incidence of PAH is between 2.0 and 7.6 cases per million adults per year and its global prevalence ranges from 11 to 26 per million which brings about elevated pulmonary vascular resistance and PA pressure while untreated it will progress to right ventricular failure and death.
Fig.1 A diagram for demonstrating the process of PAH. (Boucherat, O., et al., 2022)Pathogenesis of Pulmonary Arterial Hypertension (PAH)
The molecular pathogenesis of pulmonary hypertension is a complex and multi-factorial process but can be summarized in several key features: inflammation, alteration in angiogenic response, metabolic changes, genetic or epigenetic abnormalities, effects of sex and sex hormones, and right ventricular abnormalities. PAH is driven by genetic and epigenetic mechanisms that are involved in the establishment of the disease. The leading genetic defect is the BMPR2 mutation.
Fig.2 Current therapies and new therapeutic targets for PAH. (Johnson, S., et al., 2023)Therapeutics Development for Pulmonary Arterial Hypertension (PAH)
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Artesunate | Inhibiting inflammatory processes, resulting in vasodilation and a reduction in pulmonary vascular resistance. | ATP2A1, SERCA2 | NCT06872112 | Phase I |
| F230 tablets | A selective endothelin receptor antagonist for reducing pulmonary arterial pressure. | ETRs | NCT06899815 | Phase I |
| APL-9796 | It binds to a protein known as ZIP12 and inhibits its activity, which demonstrates potential as a therapy for pulmonary hypertension. | SLC39A12 | NCT06846554 | Phase II |
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
Dedicated to changing the paradigm of therapy for rare cardiovascular conditions such as PAH, we provide fully integrated, one-stop drug discovery and development drug service. From diagnostics and therapeutics to disease modeling, we offer researchers and scientists the tools and resources necessary to drive new discoveries and accelerate breakthroughs.
Therapeutic Development Services
Animal Model Development for PAH
Animal models are critical models to interrogate the pathophysiology of PAH, explore disease progression as well as test the effectiveness and safety of potential therapies in a regulated setting. Our team of specialists offers bespoke animal model development services to enable accurate and reproducible models and enable researchers to expedite drug discovery and more effective therapies to the bedside.
Animal models are used to mimic the pathological environment of the disease by administering monocrotaline or exposing them to continuous hypoxia.
- Monocrotaline (MCT)-induced model
- Sugen/Hypoxia-induced model
- Other models
Genetic manipulation is employed to generate models of PAH by deletion of, or overexpression of specific genes known to be related to the disease.
- BMPR2 transgenic/knockout model
- Caveolin-1 knockout model
- Other models
Protheragen offers complete preclinical services covering pharmacokinetics study and a span of drug safety assessment using state-of-the-art technology. Through the incorporation of these key elements into our process, we facilitate a seamless journey from discovery to application whilst maximizing the intimate fit between efficiency and effectiveness of the development journey. Get in touch with us to find out how we can help with your R&D requirements.
References
- Boucherat, Olivier et al. "The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure." Circulation research 130.9 (2022): 1466-1486.
- Johnson, Shelsey et al. "Pulmonary Hypertension: A Contemporary Review." American journal of respiratory and critical care medicine 208.5 (2023): 528-548.
For research use only, not for clinical use.