Non-Alcoholic Steatohepatitis (NASH)
Non-alcoholic steatohepatitis (NASH) is a type of liver disease characterized by the accumulation of fat in the liver along with inflammation and liver cell damage. Developing targeted therapies for NASH is an important goal due to the increasing prevalence and severity of this condition worldwide. Our company can provide related services to help you research related mechanisms and therapeutic options for NASH.
Introduction to NASH
It is not related to alcohol consumption and is often referred to as a "silent" liver disease as it may not cause symptoms in its early stages. However, if left untreated, NASH can progress to more severe liver conditions such as cirrhosis, liver failure, and hepatocellular carcinoma (HCC), and may cause complications such as cardiovascular disease (CVD), chronic kidney disease (CKD), dementia and so on. Due to unique genetic susceptibility and traits, individuals may exhibit different NASH phenotypes, the personalized approach to treating NASH is essential to address the diverse phenotypes and underlying factors contributing to the disease in each individual (Fig.1).
Fig.1 The progression of NASH. (Xu, X., et al., 2022)Pathogenesis of NASH
NASH is believed to be linked to a combination of factors such as obesity, insulin resistance, high levels of fat in the blood, and genetics. These factors can lead to the accumulation of fat in the liver, which can trigger inflammation and damage to liver cells. Furthermore, the gut-liver axis and gut microbiota destruction is key drivers in the pathogenesis of NASH. Dysbiosis of the gut microbiota, along with increased intestinal permeability, leads to the translocation of bacterial products such as lipopolysaccharides (LPS) into the bloodstream, triggering systemic inflammation and insulin resistance of NASH.
Diagnostics Development of NASH
- Imaging Diagnostics
Non-invasive imaging techniques such as ultrasound, controlled attenuation parameter technique (CAP), magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and other nuclear magnetic techniques can help to visualize the presence of fatty liver.
- Gene Diagnostics
Gene detection techniques such as fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) are promising tools in the fight against NASH. An example of a gene mutation associated with NASH is the PNPLA3 gene mutation.
Therapy of NASH
Small Molecule Drug Therapy
Small molecule drugs target different pathways involved in the development and progression of NASH, such as lipid metabolism, inflammation, and fibrogenesis, leading to improvements in liver steatosis, inflammation, and fibrosis. These drugs including Lanifibranor (PPAR agonist), Firsocostat (ACC inhibitor), Obeticholic acid (FXR agonist), and pioglitazone (insulin sensitizer) can effectively inhibit the development of NASH.
Gene Therapy
Using techniques to modify genes responsible for lipid metabolism, inflammation, and fibrosis in order to treat the disease at a genetic level. AR0-HSD13 is a promising gene therapy approach by targeting the HSD17B13 gene to treating liver diseases associated with dysregulated lipid metabolism, inflammation, and fibrosis. In addition, GalNAc-siTA therapeutic also partially reversed liver inflammation, injury, and fibrosis in mice.
Monoclonal Antibody Therapy
The use of monoclonal antibodies to targets specific pathways or molecules involved in the pathogenesis of the disease represents a promising avenue. CM-101 can reduce serum biomarkers associated with fibrosis and inflammation by blocking CCL24. NGM313 targets FGFR1c/KLB, which are involved in metabolic regulation and lipid metabolism, and reduce liver fat content and improve metabolic parameters in individuals with NASH.
Targeted Intestinal Flora Microbial Therapy
Manipulating the gut microbiome composition through strategies such as probiotics, prebiotics, or fecal microbiota transplantation can help reduce intrahepatic triglycerides and pro-inflammatory cytokine levels, thereby improving liver health for NASH. Studies have shown that restoring a healthy balance of gut bacteria can positively impact metabolic function and reduce inflammation in the liver.
Our Services
Our company has a team of dedicated researchers and state-of-the-art technical resources positioning us as leaders in the field, enabling us to offer cutting-edge services in diagnostic testing, construction of animal models for research, and the development of innovative therapeutic platforms for NASH diseases. We can help you unravel the underlying factors contributing to NASH and drive the research and development of therapeutic targets specifically tailored to combat NASH.
Therapy Development Platforms
Animal Models of NASH
Our company has experience in utilizing various animal models to study NASH, including high-fat diet-induced models, genetically modified models, and methionine-choline deficient diet models. Our expertise in utilizing animal models for preclinical NASH research allows us to conduct thorough evaluations of potential therapies.
| Diet-induced Models | |
| Animals such as mice or rats are fed a diet high in fat, sugar, and cholesterol to induce obesity and metabolic dysfunction, leading to the development of NASH-like symptoms. | |
| Optional Models | HFD, WD/FD, CDAHFD, MCD |
| Chemical-induced Models | |
| Animals are exposed to chemicals such as carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) which can cause liver injury and inflammation, leading to NASH-like symptoms. | |
| Optional Models | STZ, CCL4, DEN, TAA |
| Genetically Engineered Models | |
| Animals are genetically engineered to have mutations in genes that regulate lipid metabolism, insulin sensitivity, or inflammation, which mimic the pathophysiology of NASH. | |
| Optional Models | ob/ob, db/db, Foz/foz, NEMOLPC-KO |
| Optional Species | Mice, Rats, Others |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets for NASH. These models can support your pharmacokinetics analysis and drug safety evaluation, and help you better understand the disease process and develop more effective therapeutic strategies for NASH.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Xu, X., et al. "Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)." Signal transduction and targeted therapy 7.1 (2022): 287.
- Fraile, J. M., et al. "Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease." Drug design, development and therapy 15 (2021): 3997–4009.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.