- THP-1 Macrophage Polarization Model
- T Cell/B Cell Co-Culture System
- Immortalized Chondrocyte Lines
- Synovium-Cartilage Organoid Co-Culture
- Microfluidic Joint-on-a-Chip
Solutions
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Rheumatoid Arthritis (RA)
Rheumatoid Arthritis is an example of a chronic systemic autoimmune disorder. It involves synovial inflammation, cartilage and bone destruction, and has numerous comorbidities at the same time. Protheragen tackles uncontrolled innate immunity and inflammation in rheumatoid arthritis using MyD88-targeted therapeutics.
Introduction to Rheumatoid Arthritis
The chronic disorder that is Rheumatoid Arthritis (RA) is distinguished by excessive inflammation of the joints caused by synergistic activity of both the adaptive and innate immune systems. Its prevalence is roughly around 1% on a global scale, and it is more common in women. There is notable evidence of TLR-MyD88 signaling taking part in activation of fibroblasts in the synovium, auto antibody production such as RF and ACPA, and destruction of the joint through Th17 and TNF-alpha.
Pathogenesis of Rheumatoid Arthritis
- Innate Immune Dysregulation: The activation of the TLR/MyD88 signaling, either through DAMPs or components of microorganisms, drives inflammation in the joints by the NF-kb and MAPK pathways that augment the synthesis of effector pro-inflammatory cytokines like TNF-α and IL-6 which invites and recruits additional immune cells in these regions and tissues.
- Adaptive Autoimmunity & Tissue: Autoimmunity mediated by the adaptive immune system involves tissue-self-reactive T and B lymphocytes. B cells produce autoantibodies such as ACPA, while Th17 cells secrete IL-17. This cytokine stimulates synovial fibroblasts to release MMPs and RANKL, resulting in cartilage degradation and bone resorption.
Fig.1 KIC-0101 blocking the TLR/MYD88-mediated NF-κB pathway in Rheumatoid Arthritis. (Yoon et al., 2023)MyD88-Targeted Therapeutic Development for Rheumatoid Arthritis
| Therapeutic Strategy | Mechanism of Action | Key Findings | Development Stage |
| Dual IRAK4/PIM1 Inhibitor (KIC-0101) | Blocks TLR/MyD88-mediated NF-κB and JAK/STAT pathways; synergistically suppresses IRAK4 (kinase) and PIM1 (anti-apoptotic kinase). | Ameliorates cartilage damage and inflammation in RA mice. Inhibits NF-κB nuclear translocation and ibrutinib-resistant ABC-DLBCL tumor growth. |
Preclinical |
| SIRT6 Activation | Suppresses MyD88-ERK signaling by downregulating MyD88 and ERK phosphorylation. | Low SIRT6 correlates with RA severity; SIRT6 overexpression reduces IL-1β, TNF-α, IL-17, and MCP-1 in RA-FLS and rat models. Restores synovial joint integrity. |
Preclinical |
| MyD88 Dimerization Inhibitor (ST2825) | Prevents MyD88 homodimerization, disrupting TLR/IL-1R signaling. | Arrests RA synovial fibroblast (RASF) proliferation at G0/G1 phase. Reduces invasiveness and inflammation (IL-6, TNF-α) in RA organoid models. |
Preclinical |
| SIX1 Overexpression | Silences MyD88-dependent TLR1/2 signaling by inhibiting RelA-mediated TLR1/2 transcription. | SIX1 upregulation suppresses RASF proliferation, invasion, and pro-inflammatory cytokines (TNF-α, IL-6). Attenuates cartilage damage in collagen-induced RA rats. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen develops advanced disease models for Rheumatoid Arthritis as well as offers MyD88-targeted therapeutic discovery. For MyD88 signaling modulator screening and TLR/IL-1R-driven synovial inflammation pathways, along with cartilage-bone destruction in rheumatism, we unite various in vitro and in vivo models on joint-specific platforms.
Therapeutic Discovery Platform for Rheumatoid Arthritis
Protheragen's MyD88 discovery platform for RA incorporates pathway-specific modulators with joint-immune disease models to counterbalance the disrupted innate-adaptive immune crosstalk. Through novel inhibitors, degraders, or biologics, the platform achieves preclinical validation of synovial hyperplasia and joint erosion by disrupting MyD88-dependent cytokine networks while synergizing with existing therapies.
Disease Models Development for Rheumatoid Arthritis
Protheragen offers a full range of services for preclinical modeling of Rheumatoid Arthritis, featuring cell-based models, organoid models, and animal models that capture the complex pathophysiology of this immune-mediated joint disease.
- Collagen-Induced Arthritis
- Adjuvant-Induced Arthritis
- K/BxN Transgenic Mice
- hTNF-α Transgenic Mice
- CD34+ Hematopoietic Stem Cell-Humanized Mice
Through the treatment options framework for Protheragen, MyD88 related diseases are pursued aggressively. This is done by building comprehensive proposal tools ranging from disease model development, pharmacokinetics and drug safety evaluation, and other focus areas including investigator-initiated trials that aim to expedite the primary assessment stage.
If you are interested in our services, please don't hesitate to contact us.
References
- Gomes da Silva, I. I. F., et al. "Is There an Inflammation Role for Myd88 in Rheumatoid Arthritis?" Inflammation 44.3 (2021): 1014-22.
- Yoon, S. B., et al. "A Novel Irak4/Pim1 Inhibitor Ameliorates Rheumatoid Arthritis and Lymphoid Malignancy by Blocking the Tlr/Myd88-Mediated Nf-Kappab Pathway." Acta Pharm Sin B 13.3 (2023): 1093-109.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.