Macrophage Activation Syndrome (MAS)
Macrophage activation syndrome (MAS) is an uncommon but potentially life-threatening complication of systemic juvenile idiopathic arthritis (SJIA). Specialized drug and therapy development services are essential to enhance and expedite Macrophage activation syndrome research. Our company is well-equipped to address your drug and therapy development requirements in Macrophage activation syndrome therapy.
Introduction to Macrophage Activation Syndrome
Macrophage activation syndrome is a severe and potentially life-threatening condition characterized by excessive activation of macrophages and T cells, leading to a cytokine storm and multi-organ dysfunction. It is most commonly associated with rheumatic diseases, especially juvenile idiopathic arthritis, but can also be triggered by infections, malignancies, and in individuals with other autoimmune conditions. Recent literature suggests that MAS has an incidence rate of approximately 0.9 to 4.2 cases per 100,000 persons per year, indicating its rarity but significant impact.
Pathogenesis of Macrophage Activation Syndrome
The development of MAS is closely linked to a cytokine storm, which can arise from high SJIA activity or viral infections. In both scenarios, elevated levels of cytokines such as IL-1, IL-6, IL-18, and TNF-α play a significant role. Viral infections trigger the recognition of pathogen-associated molecular patterns (PAMPs) by toll-like receptors (TLRs), leading to further cytokine secretion and exacerbating inflammation. Additionally, infection-induced activation and proliferation of CD8+ T cells and NK cells and defects in their cytolytic activity contribute to hyperinflammation, ultimately leading to the activation of macrophages and tissue damage characteristic of MAS.
Fig. 1"Cytokine storm" and the development of macrophage activation syndrome (MAS).(Schulert, G.S. and Grom, A.A., 2015)
Diagnosis Development of Macrophage Activation Syndrome
The latest literature highlights the diagnostic challenges surrounding Macrophage activation syndrome, including the diversity of symptoms and signs and the overlap with similar conditions such as infections and systemic inflammatory response syndrome. To overcome these challenges, researchers are actively exploring new biomarkers, such as lysosomal enzymes, cytokines, and cell surface molecules, which may improve the early detection of MAS.
Therapy Development of Macrophage Activation Syndrome
Small molecule drugs target specific signaling pathways or cellular processes involved in MAS pathogenesis. Anakinra: This interleukin-1 receptor antagonist blocks the activity of IL-1, which plays a crucial role in MAS. Tocilizumab: A monoclonal antibody targeting the IL-6 receptor, tocilizumab inhibits IL-6 signaling, which is elevated in MAS individuals.
Monoclonal antibodies specifically target proteins or receptors involved in MAS pathogenesis. Canakinumab: A monoclonal antibody targeting IL-1β, canakinumab has been approved for the therapy of certain autoinflammatory diseases and has shown efficacy in MAS. Infliximab: This mAb targets TNFα, which is elevated in MAS, and has been used in refractory cases.
Cell-based therapies involve the infusion of immune cells or stem cells to modulate the immune response in MAS. Mesenchymal stem cells (MSCs): MSCs possess immunomodulatory properties and have shown promise in studies for treating MAS. Regulatory T cells (Tregs): Infusion of ex vivo expanded Tregs may help restore immune balance and suppress hyperinflammation in MAS.
Gene therapies aim to modify gene expression or function to correct underlying genetic defects or modulate immune responses in MAS. CRISPR/Cas9 gene editing technology holds promise for correcting genetic mutations associated with MAS or modifying immune cell function. Lentiviral gene therapy: Lentiviral vectors can deliver therapeutic genes to target cells, potentially modulating immune responses in MAS.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Macrophage activation syndrome therapy strategies and ensure robust support throughout the process.
Platforms of Macrophage Activation Syndrome Therapy Development
Animal Models of Macrophage Activation Syndrome
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to MAS therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Induced Animal Models | ||
| We provide diverse model choices customized to meet specific research needs related to Macrophage activation syndrome. | ||
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| Syngeneic Models | ||
| Syngeneic models have become invaluable tools in preclinical research. Our company offers a comprehensive range of services in syngeneic model development. | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Macrophage activation syndrome. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Schulert, G.S. and Grom, A.A., "Pathogenesis of macrophage activation syndrome and potential for cytokine- directed therapies." Annu Rev Med, (2015). 66: p. 145-159.
- Andersson, U., "Hyperinflammation: On the pathogenesis and treatment of macrophage activation syndrome." Acta Paediatr, (2021). 110(10): p. 2717-2722.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.