Giant Cell Myocarditis
Giant cell myocarditis represents a unique and rare inflammatory condition of cardiac muscle which is fatal in most cases caused by some unknown reason, defined by extensive necropolis degeneration of the myocardial fibers. At Protheragen, we facilitate advanced preclinical research services focused on rare cardiovascular conditions such as myocardial giant cell inflammation, unlocking immense potential in drug development and discovery.
Overview of Giant Cell Myocarditis
Giant cell myocarditis is an infrequent form of T lymphocyte-activated inflammatory disease of the heart muscle that affects younger populations, is frequently aggressive in onset, and may be life-threatening. Often, the symptoms include acute congestive heart failure, cardiogenic shock, uncontrollable ventricular arrhythmias, and/or complete atrioventricular heart block. The detection rate of 0.13 cases per 100,000 persons per year, which is in all likelihood underestimating the burden of the disease given the minimal window for diagnosing the disease antemortem.
Fig.1 Studies relating to giant cell myocarditis. (Hu, Z., et al., 2023)Pathogenesis of Giant Cell Myocarditis
Typically, giant cell myocarditis is understood to develop as the result of a T-lymphocyte mediated inflammatory process involving the heart muscle. Interferon-γ is produced by CD4-positive T cells which then leads to macrophages releasing nitric oxide and tumor necrosis factor. In giant cell myocarditis, the presumed mechanism of worsening underlying hemodynamic compromise is due to the increased production of nitric oxide synthase and formation of nitrite radicals.
Fig.2 Diagnostic outcomes of individuals with giant cell myocarditis. (Bang, V., et al., 2021)Therapeutics Development for Giant Cell Myocarditis
| Drug Names | Targets | Mechanism of Action | Research Phase |
|---|---|---|---|
| Antithymocyte globulin | / | Quick drop in T cells. | Approved |
| Prednisone | GR | Binds and activates particular nuclear receptors which modifies transcription and decreases inflammation by suppressing the synthesis of proinflammatory cytokines. | Approved |
| Cyclosporine | CaN | Inhibits IL-2-induced T-cell activation. | Approved |
| Mycophenolate mofetil | IMPDH | De novo purine synthesis inhibitors have an impact on the synthesis of DNA in T and B lymphocytes. | Approved |
| GSK484 | NETosis | An inhibitor of NETosis reduces giant cell myocarditis inflammation in animal models. | Preclinical |
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
The emphasis we place on excellence and translational applicability aids us in providing a smooth shift from preclinical proof-of-concept to subsequent trials. Screening of therapeutic candidates, sophisticated disease modeling, robust pharmacokinetic profiling, safety assessment, and diagnostic development are all components of our fully integrated platform which addresses the unique challenges posed by rare diseases like giant cell myocarditis.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Giant Cell Myocarditis
Aimed at precise therapeutic assessments, we provide tailored animal model development services for giant cell myocarditis utilizing trained competencies and technological proficiency. Furthermore, our responsive study frameworks permit stepwise refinements of therapy dosing and combination strategies.
Genetically Engineered Animal Model
Gene editing or transgenic animals exhibit giant cell myocarditis-like pathology which allows for examining the immune system dysregulation and cardiomyocyte damage in controlled genetic environments.
Optional models:
- HLA-DQ8 transgenic model
- PD-1/PD-L1-deficiency model
- TCR-M transgenic model
- Other models
Induced Animal Model Development
In animals, processes like anti-myosin antibodies, many viruses, or some chemicals induce immune responses which result in hallmark multinucleated giant cell infiltration, mimicking giant cell myocarditis.
Optional models:
- Cardiac myosin-induced model
- Coxsackievirus B3-induced model
- α-MyHC/CFA model
- Other models
Collaborating with various institutions, biotechnologists, and pharmaceutical companies enables Protheragen to advance cardiovascular therapeutics, which are inadequately remedied, for actual therapy research and use. Be your strategic partner in solving the intricate puzzles of rare cardiovascular diseases and reach out now so that we can get customized answers for your pipeline.
References
- Hu, Zhan et al. "Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis." iScience 26.7 (2023): 107162.
- Bang, Vigyan et al. "Management of Patients with Giant Cell Myocarditis: JACC Review Topic of the Week." Journal of the American College of Cardiology 77.8 (2021): 1122-1134.
For research use only, not for clinical use.