Metabolic Diseases

Metabolic disorders fall under a wide-spanning group of chronic diseases that create a disruption in normal metabolism, including the process of energy extraction from food. One of the major contributing disorders is non-alcoholic fatty liver disease coupled with type two diabetes. Protheragen is actively pioneering innovative compounds and therapeutic strategies that target the MyD88 pathway, aiming to address critical unmet needs in the research and preclinical development of solutions for metabolic diseases.

Overview of Metabolic Diseases

Disruption of the normal metabolic processes in the body creates complex chronic conditions termed as metabolic diseases. These disorders tend to have insulin resistance, hyperglycemia, lipid accumulation, and a chronic low-grade inflammatory response. There is a growing concern around the prevalence of these diseases due to obesity, sedentary lifestyle, and hereditary factors. There is a need to focus on these diseases due to their public health concern, their widespread prevalence, and the severe complications that follow in the form of cardiovascular diseases along with organ failure.

MyD88 in Metabolic Diseases Pathogenesis

The growth of these diseases is associated with the state of chronic, low-grade inflammation, referred to as metaflammation. MyD88, Myeloid Differentiation Primary Response 88, is pivotal in this connection as He serves as the pivotal adaptor protein for the vast majority of TLRs (Toll-like Receptors) as well as the Interleukin Receptor (IL-1R) family. His role is critical as he enables the MyD88 pathways to convey metabolic signals for the production of insulin.

Fig.1 The signaling pathway through which NK-derived exosomal miR-1249-3p regulates insulin resistance in type 2 diabetes mice. (W. Luo et al., 2022)

The MyD88 mediated pathways of TLRs and IL-1R are, in many metabolic disorders, responsible for the increase of insulin resistance and tissue destruction with MyD88's assistance. In non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, excess nutrients and toxins lead to the liberation of DAMPs (damage associated molecular patterns) or gut derived products that activate metabolic and immune TLRs. These cells signal MyD88 and in turn, the cells produce copious amounts of pro inflammatory cytokines, TNF-α and IL-1β. Metabolic dysfunction is greatly exacerbated by these events. MyD88 can be regarded as the inflammatory pathways target of choice to alter and remove the metabolic pathology.

Targeting MyD88 for the Therapeutic Development in Metabolic Diseases

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 provides comprehensive, single-point MyD88 targeted preclinical services for metabolic diseases. We design custom disease model and therapeutics including targeted refractoriness, thus streamlining the preclinical phase with focused therapeutic discovery and providing custom-tailored project services.

MyD88-Targeted Metabolic Diseases

MyD88 pathway biology informs drug development and research efforts for metabolic diseases where MyD88 is critical. It is Protheragen's strength in understanding the pathobiology of each disorder that enables the company to undertake the development of MyD88-targeted metabolic therapies for:

• Diabetic Nephropathy
• Hyperuricemia

• Non-Alcoholic Fatty Liver Disease (NAFLD)
• Type 2 Diabetes (T2D)

Therapeutic Discovery Platform for Metabolic Diseases

Protheragen's robust therapeutic discovery services encompass the entire spectrum of drug discovery and preclinical advancement, with a specific emphasis on MyD88-related targets:

• Small Molecule Inhibitors
• Monoclonal Antibodies

• siRNA Development
• Mimetic Peptides

Disease Models Development for Metabolic Diseases

For the precise assessment of MyD88-targeted therapeutic candidates' efficacy and safety, Protheragen provides a wide array of advanced disease model development services.

• Cell-based Models Development
• Organoid Models Development

• Animal Models Development

Protheragen's end-to-end capabilities streamline the drug development pipeline, from initial target identification and disease modeling to in-depth disease model development to in-depth 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

• Luo, W., et al. "Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting Myd88 and Inhibiting Myd88-Dependent Inflammation." Adv Sci (Weinh) 9.31 (2022): e2202590.
• Wang, Y., et al. "Natural Killer Cell-Derived Exosomal Mir-1249-3p Attenuates Insulin Resistance and Inflammation in Mouse Models of Type 2 Diabetes." Signal Transduct Target Ther 6.1 (2021): 409.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.