Pulmonary Veno-occlusive Disease (PVOD)
Pulmonary veno-occlusive disease (PVOD) is an unusual disease and a rare cause of pulmonary arterial hypertension (PAH) with marked remodeled small pulmonary veins and capillary involvement. As a leader in comprehensive drug discovery and development services, Protheragen is well-positioned to help expedite therapeutics in rare cardiovascular diseases. We provide a complete and fully end-to-end solution for PVOD research, a deadly disease with no therapy options.
Introduction to Pulmonary Veno-occlusive Disease (PVOD)
Pulmonary veno-occlusive disease (PVOD), also referred to as PAH with overt features of venous/capillary involvement, occurs due to significant involvement of the small pulmonary veins and capillaries, which results in elevated pulmonary vascular resistance and right heart failure. PVOD is distinguished from PAH by a greater male/female ratio, greater tobacco use history, lower resting arterial oxygen tension, reduced diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-minute walk test.
Fig.1 The typical histopathologic findings of PVOD. (Deshwal, H., et al., 2025)Pathogenesis of Pulmonary Veno-occlusive Disease (PVOD)
Certain environmental risk factors have been linked to the development of PVOD, including organic solvent exposure and chemotherapy, particularly mitomycin. Heritable forms of PVOD result from biallelic mutations in the EIF2AK4 gene, which has an autosomal recessive inheritance pattern. The EIF2AK4 gene encodes for GCN2 (general control nonderepressible 2), which is one of four kinases that phosphorylate the α-subunit of eIF2, the eukaryotic translation initiation factor 2. This protein modulates general translation in response to specific cellular stresses, for example, during the deprivation of amino acids.
Therapeutics Development for Pulmonary Veno-occlusive Disease (PVOD)
| Drug Name | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| ASC transplantation | Releasing beneficial factors that inhibit pulmonary vascular remodeling, inflammation, and right ventricular hypertrophy. | / | Preclinical |
| Amifostine | A cytoprotective agent may prevent or mitigate chemotherapy-induced PVOD by acting as a free radical scavenger and defending endothelial cells against injury from specific cytotoxic agents. | TNSALP | Preclinical |
| Epoprostenol | A potent vasodilator, platelet aggregation inhibitor, and inhibitor of smooth muscle proliferation. | Prostacyclin receptor | Approved |
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
One-stop services of our company capitalize on state-of-the-art technologies and in-depth understanding of the pathophysiology to discover new biomarkers, guide the development of targeted therapeutics, and create models of disease. These models are indispensable to dissect disease mechanisms and to robustly assess the efficacy and safety of potential drug candidates before undertaking testing in humans. Besides these services, we also offer dedicated assistance in pharmacokinetics and safety studies.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for PVOD
Because PVOD is rare and complex in its pathogenesis, there are several barriers to the successful establishment of such an animal model. We are committed to offering a full range of custom animal model creation services to assist in your research of difficult diseases such as PVOD.
Mitomycin C (MMC)-induced Model
Intraperitoneal administration of Mitomycin C in animals to induce PVOD-like phenotypes is currently one of the most established and widely used animal models for PVOD.
Animals with a homozygous deletion in GCN2 spontaneously develop increased right ventricular systolic pressure and exhibit features mimicking human PVOD.
Protheragen's end-to-end services span the entire drug discovery and development continuum, providing a clear and smooth journey from concept to application. Our focused teams are laser-focused on designing and conducting these pivotal studies, which provide the data required by regulators, all of which leads to the potential of life-changing breakthroughs for those suffering from rare cardiovascular disease, including PVOD. Please contact us to know if you are interested in our services.
References
- Lechartier, Benoit et al. "Pulmonary veno-occlusive disease: illustrative cases and literature review." European respiratory review: an official journal of the European Respiratory Society 33.171 (2024): 230156.
- Deshwal, Himanshu et al. "Pulmonary veno-occlusive disease: a clinical review." Breathe (Sheffield, England) 21.1 (2025): 240098.
For research use only, not for clinical use.