Allergic Diseases
Allergic diseases are a range of hypersensitive reactions caused by benign environmental factors. These illnesses are characterized by excessive inflammation caused by allergies and a heightened response of the immune system which results in chronic inflammation and weakening of different organ systems. Protheragen is actively engaged in pioneering innovative compounds and therapeutic strategies that target the MyD88 pathway, aiming to address the critical unmet needs in the research and preclinical development of solutions for allergic diseases.
Overview of Allergic Diseases
They are chronic disorders of the immune system which stem from anomalous response to the most common environmental and biological factors such as: pollen, dust, pet hair, and even food. Immune systems failing to recognize benign factors develop hypersensitivity which leads to inflammation and tissue damage in an organism. Asthma and skin allergies are good examples for uncontrolled allergic reactions and their contribution to someone's quality of life. This is triggered by the combination of genetic factors and their environmental influences.
MyD88 in Allergic Pathogenesis
A Type 2 immune response resulting in the activation of mast cells, basophils, eosinophils, and the production of IgE antibodies signifies the immune response in the pathogenesis of allergic diseases. Myeloid Differentiation Primary Response 88, (MyD88), plays an essential role in one of the immune response signaling pathways in allergic diseases. For the majority of signaling pathways related to Toll-like Receptors (TLRs) and the interleukin-1 receptor (IL-1R) family, MyD88 acts as an essential adaptor protein.
Fig.1 PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma. (Ma, B., et al., 2021)MyD88 pathways are of notable importance in several allergic disorders, where improper activation of TLR-IL-1R/MyD88 pathways is often considered as an underlying factor contributing to the chronic inflammatory condition. For example, some allergens are capable of eliciting the release of DAMPs or engaging specific immune cell TLRs, setting off MyD88 signaling pathways. Such pathways lead to an imbalance in the production of crucial pro-inflammatory cytokines and chemokines, setting into motion the allergic inflammatory cascade seen in asthma and several skin disorders. MyD88 targeting is, therefore, believed to offer an insightful avenue of inquiry to help control pathologic allergic immune reactions.
Targeting MyD88 for the Therapeutic Development in Allergic Diseases
| Drug Name | Indication | Mechanism of Action | Key Experimental Results & Remarks | Development Stage |
| TJ301 (BMS-986104) | Atopic Dermatitis, Asthma | Blocks MyD88 homodimerization, inhibits TLR/IL-1R downstream NF-κB and MAPK pathways | In mouse models, reduced IL-6/TNF-α levels significantly; Phase I terminated due to liver toxicity, but mechanism validation was effective | Phase I |
| Unnamed BB-loop Inhibitor | Allergic Rhinitis, Asthma | Targets MyD88 BB-loop domain, blocks TIR-TIR interaction, enhances type I IFN antiviral response | Reduced Th2 cell differentiation, increased Treg proportion; reduced airway hyperreactivity in animal models | Preclinical |
| pMyD88-shRNA Liposome | Asthma | Silences MyD88 gene, blocks DC-mediated Th2 polarization | Liposome delivery efficiency high; reduced IL-4/IL-13 levels in lung tissue, but carries risk of systemic immunosuppression | 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 delivers complete, integrated solutions for developing innovative compounds and therapies that target MyD88 in allergic diseases. Through specialized therapeutic discovery and disease model development aligned with customer needs, we expedite guided project in preclinical development stages.
MyD88-Targeted Allergic Diseases
Exploiting the MyD88 pathway biology, Protheragen actively sponsors the R&D of compounds for a broad range of allergic diseases where MyD88 is a critical component. Our team's comprehensive knowledge of every condition's intricate pathological profile enables Protheragen to provide tailored solutions, advancing the discovery and development of effective MyD88-targeted strategies for:
- Allergic Rhinitis
- Atopic Dermatitis
Therapeutic Discovery Platform for Allergic Diseases
Protheragen's therapeutic discovery services provide robust, comprehensive support across the entire spectrum of drug discovery and preclinical advancement, with a dedicated focus on MyD88-related targets:
Disease Models Development for Allergic Diseases
For the precise assessment of MyD88-targeted therapeutic candidates' efficacy and safety, Protheragen provides a wide array of advanced disease model development services, including:
Protheragen offers specialized, integrated preclinical development services, focusing on advancing MyD88-targeted therapeutic candidates for allergic diseases. Our end-to-end capabilities streamline the drug development pipeline, from initial target identification and disease model development to in-depth pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed at expediting the primary assessment stage.
Contact us today to explore collaboration opportunities.
References
- Athari, S. S. "Targeting Cell Signaling in Allergic Asthma." Signal Transduct Target Ther 4 (2019): 45.
- Ma, B., et al. "Pi3k/Akt/Mtor and Tlr4/Myd88/Nf-Kappab Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma." Inflammation 44.5 (2021): 1895-907.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.