Psoriasis
Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by hyperproliferation of keratinocytes, immune dysregulation, and systemic inflammation. Protheragen delivers targeted therapeutic development centered on MyD88 signaling modulation to address the inflammatory and autoimmune pathways driving psoriasis pathogenesis.
Introduction to Psoriasis
Psoriasis is a heterogenous dermatologic condition elicited by an imbalance in the interactions of the innate and adaptive immune systems. It has an approximate global prevalence of 2-3% with people living in colder regions experiencing it more. There is now significant data supporting the role of innate immune system activation and hyperactivity of the Th17/IL-23 axis in sustaining plaque formation, synovial inflammation (psoriatic arthritis), and other systemic comorbidities.
Pathogenesis of Psoriasis
Psoriasis is a consequence of autoimmune dysregulation which leads to excessive keratinocyte proliferation and uncontrolled immune cell infiltration. The major mechanisms include, activation of TLRs by self-nucleic acids or components of microbes resulting in MyD88 dependent activation of NF-kB and cytokine production. IL-23/IL-17 axis driven polarization of Th17 cells with consequent overproduction of TNF-a, IL-22, and antimicrobial peptides. Inflammation in the dermis caused by a host of dendritic cells, neutrophils, and macrophages which in turn perpetuate epidermal hyperplasia and angiogenesis.
Fig.1 Proposed model of the NETs-TLR4/IL-36R-keratinocyte amplification loop in psoriasis. (Lu et al., 2023)MyD88-Targeted Therapeutic Development for Psoriasis
| Therapeutic Strategy | Mechanism of Action | Progress & Challenges | Development Stage |
| MyD88 Inhibitory Peptide (MyDIP2–4) | Binds to MyD88's TIR domain, blocking homodimerization and downstream signaling. | IC50 = 2.6 μM for MyD88 interaction. Reduced psoriasis severity (PASI scores) in IMQ-induced mice. Suppressed IL-17 and epidermal thickening. |
Preclinical |
| ABIN-1 in Dendritic Cells (DCs) | Restricts MyD88-dependent TLR signals by inhibiting NF-κB/MAPK activation and IL-23 production. | ABIN-1-deficient DCs overproduce IL-23. DC-specific MyD88 deletion rescues psoriasiform lesions in mice. Links ABIN-1 to IL-23/Th17 axis dysregulation. |
Preclinical |
| Andrographolide (Andro) | Induces autophagic degradation of MyD88, blocking TRAF6 recruitment and cytokine release. | Alleviates IMQ-induced psoriasis via MAP1LC3B-dependent MyD88 degradation. Reduces IL-23/IL-1β in skin and BMDCs. No effect in MAP1LC3B-KO mice. |
Preclinical |
| MyD88 Inhibitory Peptide (MyDIP2–4) | Binds to MyD88's TIR domain, blocking homodimerization and downstream signaling. | IC50 = 2.6 μM for MyD88 interaction. Reduced psoriasis severity (PASI scores) in IMQ-induced mice. Suppressed IL-17 and epidermal thickening. |
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's services include MyD88-targeted therapeutic discovery, as well as advanced disease models development for Psoriasis. Our platform encompasses skin-specific in vitro and in vivo models for high throughput screening of MyD88 signaling modulator, TLR/IL-1R keratinocyte cutaneous immune activation and plaque formation modulators, as well as plaque formation.
Therapeutic Discovery Platform for Psoriasis
Protheragen's MyD88 discovery platform for psoriasis was developed with skin-immune disease models and modulators that focus to counterbalance the interplay of adaptive and innate immune systems. The platform aims to expedite preclinical validation psoriatic plaque formation while disrupting MyD88-dependent cytokine network and epidermal hyperproliferation by novel inhibitors, degraders or biologics, and current therapeutic regimens.
Disease Models Development for Psoriasis
Protheragen provides a complete set of services for preclinical modeling of psoriasis such as cell-based models, organoid models, and animal models that describe the multi-factorial pathophysiology of the immune-mediated skin disorder. These models capture Psoriasis mechanisms such as skin inflammation, epidermal overgrowth, and immune dysregulation for the purpose of testing prospective therapies intended to block TLR/IL-1R-MyD88 signaling.
- HaCaT keratinocyte-immune cell co-cultures
- Primary human keratinocytes
- 3D human skin organoids
- Psoriatic plaque-mimetic systems
- IMQ (Imiquimod)-induced psoriasis-like mice
- IL-23-overexpressing transgenic mice
- AGR129 mice
- K14-VEGF Transgenic Mice
Protheragen aggressively pursues MyD88 related diseases through treatment options framework and builds comprehensive proposal tools ranging from disease model development, pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed at expediting the primary assessment stage.
If you are interested in our services, please don't hesitate to contact us.
References
- Liu, M., et al. "Targeting Myd88: Therapeutic Mechanisms and Potential Applications of the Specific Inhibitor St2825." Inflamm Res 72.10-11 (2023): 2023-36.
- Liu, Y., et al. "Myd88 in Myofibroblasts Enhances Nonalcoholic Fatty Liver Disease-Related Hepatocarcinogenesis Via Promoting Macrophage M2 Polarization." Cell Commun Signal 22.1 (2024): 86.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.