Recent advancements in immunotherapy have opened new avenues for the treatment of psoriasis, particularly through targeting the MyD88 signaling pathway. Ace Therapeutics specializes in providing a full range of services to support the development of MyD88 inhibitors.

Role of MyD88 Signaling Pathway in Psoriasis

As a critical part of the innate immune response, the MyD88 (myeloid differentiation primary response gene 88) signaling pathway functions downstream of various Toll-like receptors (TLRs). In psoriasis, TLRs, particularly TLR7, play a role in in activating dendritic cells (DCs) and the following inflammatory cascade. This pathway facilitates the secretion of pro-inflammatory cytokines, such as IL-8 and TNF-α, which exacerbate the inflammatory response and contribute to the pathogenesis of psoriasis.

Recent studies indicate that MyD88 serves as a pivotal mediator in the interplay between innate and adaptive immunity in psoriasis. Inflammatory perpetuation in skin lesions is mechanistically linked to MyD88-mediated augmentation of neutrophil and DC infiltration. By inhibiting MyD88, it is possible to attenuate the inflammatory signals that drive psoriasis, offering a targeted approach to treatment.

Fig. 1 A novel mode of targeting TLR signaling by Andro-driven autophagic proteolysis of MyD88. (Shao F, et al., 2016)

What Can We Do for the Development of MyD88 Inhibitors?

At Ace Therapeutics, we are committed to offering a comprehensive suite of services tailored to assist clients in the development of MyD88 inhibitors for psoriasis. Our expertise encompasses various stages of drug development, providing clients with the necessary support to bring their therapeutic candidates from concept to preclinical validation.

Target Validation and Mechanistic Studies

We conduct in-depth studies to validate MyD88 as a therapeutic target. This includes using genetic models (e.g., MyD88 knockout mice) and pharmacological approaches to elucidate the role of MyD88 in psoriasis models, helping our clients understand the mechanism of action of their compounds.

In Vitro Assays

• Cytokine Release Assays: Utilizing ELISA and multiplex assays to measure cytokine levels in cell cultures after treatment with MyD88 inhibitors.
• Cell Viability and Proliferation Assays: Assessing the effects of inhibitors on keratinocyte and immune cell proliferation, which are critical in the pathology of psoriasis.

In Vivo Efficacy Studies

• Psoriasis Models: Utilizing imiquimod-induced mouse models to study the impact of MyD88 inhibition on skin inflammation and pathology.
• Pharmacokinetic and Pharmacodynamic Studies: Analyzing how the inhibitors are absorbed, distributed, metabolized, and excreted in animal models, providing essential data for the development of safe and effective therapies.

Biomarker Development

We assist clients in identifying and validating biomarkers that can be used to measure the efficacy of MyD88 inhibitors in preclinical models. This includes exploring gene expression profiles and protein levels associated with MyD88 signaling.

The development of MyD88 inhibitors for psoriasis presents a significant opportunity for therapeutic advancement. Ace Therapeutics is committed to providing comprehensive preclinical services to support the development of these innovative treatments, leveraging our expertise and resources to help our clients achieve their research objectives. Contact us today to learn more about how we can assist you in your drug development journey.