Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA) is a persistent autoimmune disorder that predominantly impacts the pediatric and adolescent populations. As a leading organization specializing in the development of therapeutic solutions, our company stands at the forefront of advancements in JIA therapy development.
Introduction to Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatoid arthritis (JRA), is a heterogeneous group of chronic inflammatory joint disorders that manifest before the age of 16 and persist for at least six weeks. It is characterized by joint inflammation, pain, swelling, and stiffness. JIA is considered an autoimmune disease, wherein the immune system mistakenly attacks the body's own tissues, primarily targeting the synovial membrane of the joints.
The pathogenesis of JIA involves dysregulation of the immune system, leading to chronic inflammation in the joints. Abnormal activation of immune cells, including T cells, B cells, and macrophages, results in the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. These cytokines drive the recruitment of inflammatory cells and promote the production of other inflammatory mediators, leading to synovial hyperplasia, cartilage degradation, and bone erosion.
Fig.1 The local immune-inflammatory environment of oligoarticular JIA (oJIA). (La Bella S., et al., 2023)
Therapy Discovery and Development for Juvenile Idiopathic Arthritis
Biologic agents have revolutionized the therapeutics of JIA, particularly in cases where DMARDs alone are insufficient. Etanercept is a TNF-α inhibitor that has shown efficacy in reducing inflammation and improving disease outcomes in JIA cases. Moreover, abatacept, a CTLA4-Ig fusion protein, and tocilizumab, an IL-6 receptor inhibitor, are alternative biological agents that have demonstrated effectiveness in JIA. These agents may be considered for cases that do not respond adequately to TNF-α inhibitors or have specific JIA subtypes, such as refractory psoriatic JIA or JIA-related uveitis.
As part of our unwavering dedication to furthering JIA therapy, our company provides an extensive array of services pertaining to diagnostics and therapy development. Should you harbor an interest in exploring the remarkable therapeutic development opportunities we offer, we warmly invite you to click on the link provided below for further information.
Our Services
To facilitate the development and testing of new therapies, we specialize in the creation and utilization of animal models and in vitro models for JIA. These models allow us to study disease mechanisms and evaluate drug candidates in a controlled laboratory setting. By utilizing animal and in vitro models, we can accelerate the discovery and development of potential JIA therapies.
Repeated TLR-9 Stimulation Models
Dysregulation of TLR-9 (Toll-like receptor 9) signaling has been implicated in the pathogenesis of JIA. Our company offers the development of animal models that involve repeated TLR-9 stimulation to mimic the chronic inflammation observed in JIA.
IL-6 Transgenic Models
IL-6 (Interleukin-6) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of JIA. Our company provides the development of IL-6 transgenic animal models, where the IL-6 gene is overexpressed, leading to sustained activation of the immune system and joint inflammation.
IFN-γ Knockout / CFA Stimulation Models
Our company offers the development of IFN-γ knockout animal models in combination with Complete Freund's Adjuvant (CFA) stimulation. This model mimics the dysregulated immune response observed in JIA and allows us to study the interplay between IFN-γ and other immune mediators.
CD40 Stimulated Models
CD40 is a cell surface molecule involved in immune cell activation and differentiation. Our company provides the development of CD40 stimulated animal models, where CD40 signaling is enhanced, leading to increased inflammation and joint damage.
Our company offers the development of cell-based models for JIA, allowing researchers to study the interactions between different cell types involved in the disease. These models involve the isolation and culture of primary cells, such as immune cells, fibroblasts, and synovial cells.
Organoids offer several advantages over traditional cell cultures as they closely resemble the complexity of native tissues. The JIA synovial organoids we provide can be used to investigate the aberrant proliferation of synovial cells, the inflammatory response, and the impact of potential therapeutic interventions.
We conduct comprehensive preclinical studies, including pharmacokinetics, pharmacodynamics, safety, and efficacy assessments, to ensure that promising candidates meet the necessary requirements for further development. Beyond the aforementioned repertoire of services and models, our expertise extends to crafting personalized solutions and designing disease models that impeccably align with your unique needs. If our comprehensive range of offerings has piqued your interest, we wholeheartedly encourage you to connect with us without any hesitation.
References
- La Bella S., et al. "Genetic background and molecular mechanisms of juvenile idiopathic arthritis." International Journal of Molecular Sciences 24.3 (2023): 1846.
- Zaripova L. N., et al. "Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches." Pediatric Rheumatology 19 (2021): 1-14.