Asthma
An episode of asthma is characterized by wheezing, breathlessness, cough, chest tightness, and the reversible bronchoconstriction. It is caused by chronic inflammatory disease of the airways along with hyper responsiveness and inflammation. Protheragen's MyD88-targeted therapy development aims to modulate the dysregulated innate immune responses mediated by MyD88.
Introduction to Asthma
Asthma is one of the most prevalent chronic diseases around the world affecting over 300 million people and its etiology is linked to the combination of genes and environment. These triggers stimulate innate immune responses in the epithelial cells, dendric cells, and resident immune cells. New data suggests that the MyD88 dependent signaling pathway (which is triggered by TLR and/or IL-1R) has a significant role toward an inflammatory response that drives airway hyperresponsiveness, airway remodeling, and inflammation.
Pathogenesis of Asthma
Exposure to allergic agents causes damage to the airway epithelium and releases DAMPs like uric acid and ATP which activate the TLR/IL-1R-MyD88 axis in the macrophages and dendritic cells. MyD88 activates IRAK1 and 4, which in turn initiate the NF-kB and MAPK pathways for inflammation. Newer works highlight the involvement of MyD88 in epithelial-mesenchymal transition (EMT) and subepithelial fibrosis through crosstalk with TGF-β. MyD88 active within airway smooth muscle cells leads to increased hyperresponsive bronchoconstriction by increased leukotriene production.
Fig.1 Targeting cell signaling in allergic asthma Athari. (Athari, 2019)MyD88-Targeted Therapeutic Development for Asthma
Direct MyD88 Pathway Inhibition:
New approaches are being developed to inhibit MyD88 dimerization or TIR domain interaction resulting in TLR/IL-1R signaling blockade in macrophages and epithelial cell airways. New cell penetrating peptide mimetics and allosteric small molecules that inhibit IL-33/TSLP production have been developed and tested in murine models in 2023, proving reduction of Th2 inflammation and subepithelial fibrosis.
Downstream IRAK4 Modulation:
IRAK4 kinase inhibitors and PROTAC degraders are moving forward to clinical testing with MyD88's NF-κB/MAPK signaling to mast cell and smooth muscle activation. New in vivo studies with inhaled PROTAC-IRAK4 show targeted treatment for steroid-resistant asthma by blocking leukotriene production and hyper-responsiveness of airways without peripheral immune suppression.
Our Services
Protheragen provides MyD88-targeted therapeutic discovery and advanced disease models development services specifically tailored for Asthma. Our disease models enable preclinical intervention development aimed at mitigating airway innate immune activation, inflammation, hyperresponsiveness, and remodeling in asthma.
Therapeutic Discovery Platform for Asthma
Protheragen offers an integrated platform for MyD88-targeted Asthma therapeutic discovery that focuses on modulating the dysregulated innate immune response in the airways and its contribution to chronic inflammation and structural changes. The platform leverages pathway-driven disease models designed for preclinical investigation, aiming to disrupt the MyD88-dependent inflammatory cascade initiated by various asthma triggers.
Disease Models Development for Asthma
Protheragen offers extensive in vitro & in vivo models for Asthma, including cell-based models, organoid models, and animal models, enabling the comprehensive evaluation of MyD88-targeted therapeutic strategies. These models recapitulate key aspects of asthma pathogenesis, providing critical insights into therapeutic efficacy against airway inflammation, hyperresponsiveness, and remodeling.
- Th2 Cell-Epithelial Cell Co-culture Systems
- Airway Smooth Muscle Cell Activation Models
- Airway Organoid Models
- OVA/HDM-Induced Asthma Models
- Chronic Asthma Remodeling Models
- Conditional MyD88 Knockout Models
- Microbiome-Asthma Interaction Models
Protheragen advances MyD88-targeted drug discovery for asthma through end-to-end solutions. We provide comprehensive proposal tools encompassing disease model development, pharmacokinetics and drug safety evaluation, alongside support for investigator-initiated trials.
If you are interested in our services, please don't hesitate to contact us.
References
- Athari, S. S. "Targeting Cell Signaling in Allergic Asthma." Signal Transduct Target Ther 4 (2019): 45. Print.
- Shang, L., et al. "Hmgb1 Was Negatively Regulated by Hsf1 and Mediated the Tlr4/Myd88/Nf-Kappab Signal Pathway in Asthma." Life Sci 241 (2020): 117120.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.