Granulomatosis with Polyangiitis

Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare autoimmune disease characterized by inflammation of blood vessels and the formation of granulomas. Our company is committed to providing specialized autoimmune disease drug and therapy development services, including GPA.

Overview of Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA) is a systemic autoimmune disease that primarily affects small to medium-sized blood vessels, leading to inflammation and damage in multiple organs. The pathogenesis of GPA involves an aberrant immune response, resulting in the production of autoantibodies known as anti-neutrophil cytoplasmic antibodies (ANCAs). ANCAs, specifically anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies, play a crucial role in the development and progression of GPA. These antibodies bind to neutrophils and monocytes, leading to the activation of these immune cells and subsequent damage to blood vessels. GPA predominantly affects the upper and lower respiratory tracts, kidneys, and sometimes other organs such as the skin, eyes, and joints.

Diagram shows the main clinical manifestations of granulomatosis with polyangiitis (GPA).Fig.1 The main manifestations of granulomatosis with polyangiitis (GPA). (Guzman-Soto, M. I., et al., 2021)

Drug Discovery and Development for Granulomatosis with Polyangiitis

The therapy of GPA involves a combination of corticosteroids and immunosuppressants to achieve and maintain remission. Immunosuppressants, such as cyclophosphamide, methotrexate, and rituximab, are commonly used in combination with corticosteroids for induction and maintenance therapy. Cyclophosphamide, traditionally used for induction therapeutics, can be administered orally or intravenously. Moreover, methotrexate is an alternative immunosuppressant used primarily in limited/localized forms of GPA. It is less effective than cyclophosphamide and has a higher relapse rate. Rituximab, a monoclonal antibody targeting CD20, has shown promising results in severe GPA cases and relapsing patients, particularly in combination with corticosteroids.

In therapy development, we focus on the identification and development of novel therapy options for GPA. Our experienced team of researchers and scientists work tirelessly to discover and optimize potential drug candidates targeting key pathways involved in GPA pathogenesis. If you would like to find your own exclusive therapy development solution, please click the link below to learn more.

Our Services

With extensive experience and diverse platforms, our company is committed to providing cutting-edge diagnostics and therapeutic development services for granulomatosis with polyangiitis. Our state-of-the-art facilities and expertise allow us to conduct in-depth evaluations of potential therapeutic candidates, including pharmacokinetic and pharmacodynamic studies, toxicity assessments, and efficacy evaluations.

MPO-AAV Animal Models

Our company provides myeloperoxidase (MPO)-ANCA associated vasculitis (AAV) animal model development services, this model is closely mimic the pathogenesis of the disease. By utilizing genetic modification techniques, we enhance the expression of MPO and other relevant factors in neutrophils, allowing for a more accurate representation of disease progression.

PR3-AAV Animal Models

PR3-antineutrophil cytoplasmic antibodies (PR3-ANCA) are implicated in the pathogenesis of PR3-AAV. One approach involves the use of mice with a humanized immune system. By reconstituting the immune system of mice with human hematopoietic stem cells, we can create a more accurate representation of the immune response to PR3-ANCA.

Cell-Based Models

Isolating and culturing monocytes from GPA patients is a crucial step in developing cell-based models. Our experienced team of researchers is skilled in optimizing protocols for monocyte isolation from peripheral blood samples.

Organoid Models

Our company provides cutting-edge organoid model development services for GPA research. We utilize advanced protocols for generating kidney organoids from patient-derived induced pluripotent stem cells (iPSCs) or progenitor cells.

Through our preclinical research services, we aim to generate robust data on safety, efficacy, and mechanism of action, ensuring the selection of the most promising candidates for further development. In addition to the aforementioned services and models, we also provide customized solutions and develop disease models that cater specifically to your unique needs. If our services have piqued your interest, please do not hesitate to contact us.

References

  1. Guzman-Soto, Mahatma I., et al. "From head to toe: granulomatosis with polyangiitis." Radiographics 41.7 (2021): 1973-1991.
  2. Puéchal Xavier. "Granulomatosis with polyangiitis (Wegener's)." Joint Bone Spine 87.6 (2020): 572-578.
For research use only. Not intended for any clinical use.