Giant Cell Arteritis
Giant cell arteritis (GCA, also referred to as temporal arteritis) is considered a large and medium vessel vasculitis and may be seen in the cranial vessels, aorta, and great vessels. With challenging rare cardiovascular diseases like giant cell arteritis, a leader in drug discovery and drug development innovation, Protheragen provides unique preclinical services that facilitate the success of your program.
Introduction to Giant Cell Arteritis
Giant cell arteritis is an idiopathic granulomatous vasculitis of medium and large vessels; it presents various phenotypes, such as typical cranial arteritis and extra-cranial giant cell arteritis, also called large-vessel giant cell arteritis. It is the most common systemic vasculitis, occurring worldwide at between 15 and 25 per 100,000 people over the age of 50. It is a systemic rheumatic disease that is essentially never seen in adults younger than 50 years. The disease can also be a generalized one affecting the aorta and its branches with aneurysmal involvement, or abnormal stenosis of the vessel or vessels involved.
Fig.1 Cellular and molecular basis of GCA. (Paroli, M., et al., 2024)Pathogenesis of Giant Cell Arteritis
Under physiological circumstances, the arterial wall is an immunoprivileged site, the local immune cells of which preserve a tolerogenic phenotype. In giant cell arteritis, there is a loss of this tolerogenic state, and inflammation will develop and spread along with the presence of granulomatous infiltrates, neovascularization, intimal hyperplasia, and occlusion.
Evidence for a genetic contribution to the pathogenesis of giant cell arteritis is provided by variation in prevalence between ethnic groups, familial aggregation, and several genetic associations. Giant cell arteritis has a powerful genetic component; specifically with the human leucocyte antigen (HLA) region, particularly the HLA class II genes.
Fig.2 Symptom frequencies in GCA and the criteria for diagnosis. (Lyons, H. S., et al., 2020)Therapeutics Development for Giant Cell Arteritis
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Glucocorticoids | Decreasing inflammation by inhibiting the activity of the immune system, and thus dampening the liberation of the inflammatory cytokines and mediators. | GR | / | Approved |
| Bosentan | Blockade of endothelin receptors, resulting in vasodilation and possible decrease in vascular inflammation and injury. | ETA, ETB | NCT06887062 | Phase II |
| Secukinumab | By targeting IL-17A, which is a pro-inflammatory cytokine, thereby alleviating the inflammatory and immune responses of the disease. | IL-17A | NCT04930094 | Phase III |
| Methotrexate | Blocking the enzyme dihydrofolate reductase, thus interfering with the proliferation of immune cells and with the inflammation. | DHFR | NCT05623592 | 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
With our long-established skills and techniques, covering the entire research pathway, from diagnostics and therapeutics to disease model developments, we can act as your one-stop shop for all your research requirements. Our tailored services are designed to accelerate your project's trajectory, ensuring innovative and effective solutions are within reach.
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Animal Model Development for Giant Cell Arteritis
Animal models are essential for understanding the pathophysiology and therapeutic approaches of giant cell arteritis and have gained increasing appreciation in complex diseases such as giant cell arteritis. Our company is the expert in establishing custom animal models according to your specific research requirements.
Animal models of giant cell arteritis are developed by altering certain genes, such as ones associated with immune responses, to mimic the pathophysiology of the disease, and evaluate its mechanisms.
- TCR transgenic model
- Other models
The temporal artery of those giant cell arteritis individuals is introduced to nude mice in order to establish a nude mice giant cell arteritis model. Human-specific vascular responses are studied by using the human arterial tissue implanted in immunodeficient mice.
Supplement your drug discovery process, Protheragen provides comprehensive pharmacokinetic studies and intense drug toxicity screening. Our preclinical development solutions aim to have every step of your discovery process optimized with precision. Please feel free to get in touch with us to explore how we can customize our solutions for your needs.
References
- Paroli, Marino et al. "Giant Cell Arteritis: Advances in Understanding Pathogenesis and Implications for Clinical Practice." Cells 13.3 (2024) 267.
- Lyons, H S et al. "A new era for giant cell arteritis." Eye (London, England) 34.6 (2020): 1013-1026.
For research use only, not for clinical use.