ANCA-associated Vasculitides
There is a 65% increased cardiovascular disease (CVD) risk in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides individuals. CVD is the most common cause of death in individuals with ANCA-associated vasculitides. Protheragen is a reputable research service provider dedicated to providing end-to-end drug discovery and development solutions for rare cardiovascular diseases, including ANCA-associated vasculitides. We're here to help unlock the full potential of your science, and by specializing in pushing the boundaries of innovation in this complex therapeutic area.
Introduction to ANCA-associated Vasculitides
ANCA-associated vasculitides are a family of uncommon systemic necrotizing small-vessel vasculitides. It is an immune-mediated inflammation of small and medium arteries resulting in endothelial cell disruption and end-organ ischemia. It has an estimated worldwide prevalence of around 400 per million and encompasses a trio of distinct but overlapping entities: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA).
Fig.1 Frequencies of organ system involvement in GPA, MPA, and EGPA. (Sayer, M., et al., 2024)Pathogenesis of ANCA-associated Vasculitides
At the core of the pathogenesis of ANCA-associated vasculitides is the loss of B-cell and T-cell tolerance to the neutrophil proteins PR3 or MPO expressed on the surface of primed neutrophils. Priming takes place in the presence of pro-inflammatory mediators (IL-1β, IL-6, TNFα) or following the activation of complement by the alternative pathway. Autoantibodies generated by B-cells bind MPO/PR3 on the membrane of primed neutrophils, initiating neutrophil activation. In addition to neutrophils, ANCA stimulates monocytes and macrophages, also enhancing microvascular inflammation and inducing thrombosis via platelet contacts.
Fig.2 ANCA-associated vasculitides and atherosclerosis involve shared cellular pathways. (Sayer, M., et al., 2024)Therapeutics Development for ANCA-associated Vasculitides
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| NKX-019 | A CD19-targeted CAR NK cell therapy might have efficacy in immune modulation in ANCA-associated vasculitides. | CD19, IL-15 | NCT06733935 | Phase I |
| QH103 | Depletion of CD19-positive B cells and subsequent decrease in the production of pathogenic autoantibodies. | CD19 | NCT06828042 | Phase I/II |
| Avacopan | Blockade of the complement 5a receptor (C5AR) to decrease neutrophil activation and inflammation. | C5AR1 | NCT06794827 | Approved |
| YTB323 | An autologous CD19-CAR-T cell, with the function of regulating immune dysfunction in ANCA-associated vasculitides. | CD19 | NCT06868290 | 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
Protheragen specializes in ANCA-associated vasculitides research along with providing diagnostics, therapeutics, and developing disease model development services. We create accurate models of diseases and groundbreaking therapy methods using the latest technologies. Also, our pharmacokinetic evaluation and drug safety studies will always give you dependable and precise information, ensuring that your preclinical programs are scientifically rigorous and reliable.
Therapeutic Development Services
Animal Model Development for ANCA-associated Vasculitides
ANCA-associated vasculitides poses a rare but complex cardiovascular challenge. The creation of its animal models is fundamental in the progress of ANCA-associated vasculitides research as well as in therapy innovations. Understanding this need, our company provides bespoke animal model development services tailored to your research objectives.
MPO-ANCA-associated vasculitides Animal Models
- Anti-MPO ANCA transfer model
- MPO-specific splenocyte transfer model
- Bone marrow transplant model
- MPO-specific T-cell transfer model
- Other models
PR3-ANCA-associated vasculitides Animal Models
- Human anti-PR3 ANCA passive transfer model
- PR3-specific splenocyte transfer model
- NETs passive transfer model
- PTU-induced passive transfer model
- Other models
Driven by a keen desire to provide unparalleled support throughout the drug development process, Protheragen's experts work hand in hand with clients to ensure the successful navigation of rare cardiovascular disease research. We offer strategies tailored to the client's needs, standing out from the competition with our suite of preclinical services. To find out how we can assist with your unfolding research and development demands, reach out to us today.
Reference
- Sayer, Matthew et al. 'Cardiovascular Disease in Anti-neutrophil Cytoplasm Antibody-Associated Vasculitis.' Current rheumatology reports 26.1 (2024): 12-23.
For research use only, not for clinical use.