Multiple Sclerosis (MS)
Multiple Sclerosis (MS) is a chronic, autoimmune neurologic condition that results in demyelination and neurodegenerative changes in the central nervous system with sequelae of musculoskeletal and psychosocial disability. Protheragen delivers comprehensive MyD88-targeted therapeutic development, focusing on inhibitors to disrupt MyD88 signaling cascades implicated in inflammatory, autoimmune, and oncologic pathologies.
Introduction to Multiple Sclerosis
Multiple Sclerosis (MS) is a heterogenous neuroinflammatory disease driven by an autoimmune response gone wrong targeting myelin sheaths and axons. Newer epidemiological data trends suggest that there is an annual incidence of 5 to 10 cases for every 100,000 people, and this is more common towards the temperate regions. There is new evidence marking the role of the innate immune system activation and poorly regulated adaptive immune response on progression of the disease which marks the relapsing-remitting or progressive clinical phenotypes.
Pathogenesis of Multiple Sclerosis
Multiple sclerosis is rooted in autoimmune malfunction that causes deterioration of the central nervous system. It's stem from disordered T and B cells which attack the myelin sheath leading to inflammation of the nervous system and activation of microglia. Pro-inflammatory cytokines and immune cell infiltration across the blood-brain barrier and inflame demyelination and axonal injury. Recent studies have stressed the importance of innate immune pathways, particularly MyD88-dependent Toll-like receptor signaling, in perpetuating inflammatory cascades.
Fig.1 The TLR-MyD88 signaling pathway contributes to the pathogenesis of multiple sclerosis (MS). (Ban, Sato and Tamura, 2018)MyD88-Targeted Therapeutic Development for Multiple Sclerosis
| Therapeutic Strategy | Mechanism of Action | Representative Approaches | Development Stage |
| TLR Antagonists | Block TLR activation by competing with ligands or binding to TLR domains. | T2.5 (anti-TLR2 mAb), OPN-305 (anti-TLR2 mAb), IMO-3100 (TLR7/9 antagonist). | Preclinical |
| Soluble TLRs (sTLRs) | Neutralize TLR activators (e.g., LPS, viral proteins) to inhibit downstream signaling. | Soluble TLR4 or TLR9 constructs binding pathogens/ligands. | Preclinical |
| MyD88 Inhibition | Disrupt MyD88 homodimerization or downstream signaling (e.g., IRAK1 phosphorylation). | sMyD88 (short MyD88 form blocking IRAK1), BB-loop decoy peptides (TIR domain disruption). | Preclinical |
| TLR-MyD88 Pathway Modulators | Reduce pro-inflammatory cytokines (TNF-α, IL-1β) and promote remyelination. | TLR2/4/7/9 antagonists suppressing NF-κB/NLRP3; OPN-305 in EAE models. | Preclinical |
| Axon Repair/OPC Recruitment | Enhance oligodendrocyte precursor cell (OPC) infiltration and remyelination. | TLR antagonists (e.g., T2.5) shown to spare axons and promote OPC migration in models. | Experimental (preclinical) |
| TLR Antagonists | Block TLR activation by competing with ligands or binding to TLR domains. | T2.5 (anti-TLR2 mAb), OPN-305 (anti-TLR2 mAb), IMO-3100 (TLR7/9 antagonist). | 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 offers MyD88-targeted therapeutic discovery and advanced disease models development services for multiple sclerosis. Our disease models facilitate fast screening of MyD88 signaling modulators for use in neuroinflammatory disorders in order to expedite preclinical development.
Therapeutic Discovery Platform for Multiple Sclerosis
Protheragen's MyD88 targeted discovery platform for multiple sclerosis offers an integrated approach that therapeutically manages demyelination and neuroinflammation. It seeks to modulate MyD88 signaling within specific pathways through tailored disease models geared towards preclinical testing, aiming at dysregulated innate immunity within CNS pathologies and boosting the workings of previously developed therapies.
Disease Models Development for Multiple Sclerosis
Protheragen offers a full-package service for preclinical modeling of multiple sclerosis in the form of cell-based models, organoid models, and animal models, serving all the requirements. These enable detailed analysis of the processes involving demyelination, neuroinflammation, and axonal injury for thorough assessment of therapy options focusing on the pathophysiology of MS.
- Microglia-Neuron Co-Cultures
- 3D Myelinating CNS Organoids
- Blood-Brain Barrier (BBB) Mimetics
- Experimental Autoimmune Encephalomyelitis
- Cnp-Cre; Myd88fl/fl Transgenic Mice
- Zebrafish CNS Demyelination Models
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
- Sun, W., et al. "Ketogenic Diet Attenuates Neuroinflammation and Induces Conversion of M1 Microglia to M2 in an Eae Model of Multiple Sclerosis by Regulating the Nf-Kappab/Nlrp3 Pathway and Inhibiting Hdac3 and P2x7r Activation." Food Funct 14.15 (2023): 7247-69.
- Zheng, C., et al. "Inflammatory Role of Tlr-Myd88 Signaling in Multiple Sclerosis." Front Mol Neurosci 12 (2019): 314.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.