Granulomatosis with Polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis associated with inflammation of the vascular wall and peri- and extravascular granulomatosis. Rarities disease research like GPA in the cardiovascular system requires specific approaches. Protheragen is a premier preclinical research service provider that offers one-stop drug discovery and development solutions.

Introduction to Granulomatosis with Polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA) previously referred to as Wegener's Granulomatosis (WG) is a systemic necrotizing vasculitis of small and medium vessels, characteristically associated with cytoplasmic ANCA. One of the main characteristics of GPA is the presence of cytoplasmic ANCAs in 90% of forms systemic and 50% localized against proteinase 3 in most cases. GPA is also a rare disease, with an incidence of 3/100,000 population. GPA affects both sexes. Although the average age of onset is 45 years, some cases have been reported in the elderly and even in children.

Fig.1 The role of neutrophils in ANCA vasculitis. (Witko-Sarsat, V., and Thieblemont, N., 2018)

Pathogenesis of Granulomatosis with Polyangiitis (GPA)

Neutrophils are fundamental to the pathogenesis of the disease due to their expression of autoantigen proteinase 3 (PR3) and control is lost in people with GPA. People with GPA hold neutrophilic PR3 autoantibodies.

The primary histopathology changes may be as follows: it seems that cellular infiltrate, including CD4 T cells, CD8 T cells, NK cells, γδ T lymphocytes, macrophages can be found in early vascular lesion; Then granulocytes, giant cells, and granuloma formation can be observed in the media of involved arteries, especially; Finally, extensive fibrosis and intimal hyperplasia develop and may cause aortic thickening (or stenosis, occlusion), occasionally aortic dissection/aneurysm formation occurred.

Fig.2 Categorization of vasculitis by the vessel size. (Puéchal X., 2020)

Therapeutics Development for Granulomatosis with Polyangiitis (GPA)

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

From diagnostics and therapeutics right through to disease model generation, we have preclinical covered. Pharmacokinetic analysis and thorough drug safety testing that you can rely on to keep your programs moving forwards, quickly and efficiently. Our desire for quality means that potential therapeutics are manufactured to the standards of the industry, lessening risks and improving the probability of successful results.

Therapeutic Development Services

Diverse Platforms

• Small Molecule Drug Development
• Gene Therapy Development
• Therapeutic Peptide Development

• Cell Therapy Development
• Therapeutic Antibody Development
• Therapeutic Protein Development

Animal Model Development for GPA

Idealized animal models that are faithful to human disease are important to drug discovery and research and development in GPA. They allow us to learn why disease occurs, to test new drugs more efficiently and safely, and to develop methods of therapy aimed at a particular mode of action. Understanding the importance of accurate and pragmatic animal models in the research of GPA, our company supports personalized animal model development services to meet your requirements.

Induced Animal Model

Animal models of GPA are generated by immunization of animals with selected antigens or antibodies to recapitulate the pathological features of the disease.

• MPO-ANCA IgG-induced model
• Other models

• PR3-ANCA induced model

Using our vast experience and modern facilities, Protheragen provides unsurpassed quality and speed to market for your therapeutics in demand. Find out about working with us and give your research a boost. Contact us to learn how we can work with you to advance your drug discovery and development programs.

References

• Puéchal, Xavier. 'Granulomatosis with polyangiitis (Wegener's).' Joint bone spine 87.6 (2020): 572-578.
• Witko-Sarsat, Véronique, and Nathalie Thieblemont. 'Granulomatosis with polyangiitis (Wegener granulomatosis): A proteinase-3 driven disease?' Joint bone spine 85.2 (2018): 185-189.