Type 1 Diabetes (T1D)
Type 1 Diabetes (T1D) constitutes an autoimmune disease caused by a persistent inflammation that results in the immune system damaging the β-cells of the pancreas which leads to an insufficiency of insulin secretion and high blood glucose levels. Protheragen specializes in the treatment of autoimmune diseases aimed at modulating the innate defense response that controls β-cell autoimmunity and inflammation with MyD88 and develop new treatments to protect the remaining functional β-cells.
Introduction to Type 1 Diabetes
T1D is a heterogenous autoimmune disease caused by a genetic predisposition (HLA–DR/DQ alleles) and several environmental factors (like viral infections and gut dysbiosis). The global incidence rates vary from 15 to 20 per 100,000 on an annual basis with the prevalence attributed to early-life antibiotic use and gluten-containing diets. There is emerging evidence supporting the contribution of TLR-MyD88 signaling in dendritic cell activation, polarization of islet-infiltrating T-lymphocytes, and β-cell apoptosis which propels the preclinical stage of autoimmunity to clinical onset.
Pathogenesis of Type 1 Diabetes
- Triggering of innate immunity: Products from some viruses or gut bacteria containing RNA /DNA activate TLR3/7/9-MyD88 pathways in pancreatic ductus that are responsible for relaying inflammatory signals, which leads to the synthesis of pro-inflammatory cytokines.
- Autonomous dysregulated immunity: After amplification, islet inflammation secures recognition of β-cell antigens like GAD65 & Insulin through autoreactive CD8+ T lymphocytes. This is sustained by IFN-γ/IL-17 elicited by Th1/Th17 cells.
- Uncontrolled cell stress: Augmentation of antigen circulation contributes to effector cell elimination, thereby worsening the mitochondrial malfunction and exhaustion of ER, vasculature-chained auto-destructive will increase.
Fig.1 Gut Microbiota-MyD88 Axis Contributes to Stroke Aggravation in Type 1 Diabetes. (Zeng et al., 2025)MyD88-Targeted Therapeutic Development for Type 1 Diabetes
Direct MyD88-Targeted Therapies
Research is directed at certain class of small molecule MyD88 signaling inhibitors such as TAK-242 dimerization-blocking MyD88 dimerization analogs, and gene-editing weapons, the use of which in preclinical models showed reduced insulitis and maintained beta cells. Peptide-based disruptors that mimic the TIR domain of MyD88 are also promising but face challenges relating to stability, and directed delivery.
Indirect MyD88 Pathway Modulation
Such TLR antagonists like Hydroxychloroquine, which was evaluated in the first rounds of T1D trial, indirectly interfere with the activating MyD88 by restricting upstream receptors. MyD88 pathway modulators can be combined with anti-CTLA-4 and even shield the overpowering immune regulation while controlling the indiscriminate immune suppression offer plausible solutions lacking pending clinical validation.
Our Services
Protheragen's services include MyD88-targeted therapeutic discovery, as well as advanced disease models development for Type 1 Diabetes. Our platform integrates pancreas-specific in vitro and in vivo models to enable high-throughput screening of MyD88 signaling modulators, TLR/IL-1R-driven innate immune activation, and β-cell destruction mechanisms.
Therapeutic Discovery Platform for Type 1 Diabetes
Protheragen's MyD88 discovery platform for T1D leverages immune-pancreas crosstalk models to address the interplay between adaptive and innate immune systems. The platform accelerates preclinical validation of therapies aimed at disrupting MyD88-dependent pro-inflammatory cytokine networks, halting autoimmune β-cell destruction, and preserving insulin secretion through novel inhibitors, degraders, or biologics.
Disease Models Development for Type 1 Diabetes
Protheragen offers comprehensive preclinical modeling services for T1D, including cell-based models, organoid models, and animal models that recapitulate the multifactorial pathophysiology of T1D.
- Primary Human Islet Cultures
- Immortalized β-Cell Lines
- Immune Cell-β Cell Co-Culture Systems
- Human Islet Organoids
- Non-Obese Diabetic Mouse
- Streptozotocin (STZ)-Induced Diabetic Models
- B Cell Receptor Transgenic Mice
- RIP-LCMV-GP 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
- Androulidaki, A., et al. "Differential Role of Myd88 and Trif Signaling in Myeloid Cells in the Pathogenesis of Autoimmune Diabetes." PLoS One 13.3 (2018): e0194048.
- Zeng, X., et al. "Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-Myd88 Pathway in Mice." Mol Neurobiol 62.3 (2025): 3764-80.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.