Primary Sclerosing Cholangitis (PSC)
Primary sclerosing cholangitis (PSC) is a complex and rare condition that presents with multifocal bile duct stenosis and advanced liver disease. Our company's extensive experience in PSC research allows us to provide you with customized services as well as comprehensive assistance that can help you move from PSC therapy development to therapy commercialization.
Introduction to PSC
Primary sclerosing cholangitis (PSC) is a rare but serious liver disease. The incidence of PSC is low, with approximately 1-1.5 cases per 100,000 person-years, and the disease shows a predilection for men. This chronic and progressive condition is characterized by fibrous inflammatory injury of the biliary system, which can gradually develop from intrahepatic and extrahepatic bile duct inflammation to bile duct fibrosis, cirrhosis, liver failure, and even death.
Pathogenesis of PSC
Pathogenesis of PSC involves a combination of genetic, immunological, and environmental factors. Variations in the HLA complex, which plays a critical role in the immune system, have been linked to PSC. Other genes involved in immune regulation and bile acid metabolism have also been implicated in the development of the disease. The interaction between genetic susceptibility and environmental factors, such as bacterial infections or changes in gut microbiota, likely plays a role in the development of PSC (Fig.1).
Fig.1 The pathogenesis of primary sclerosing cholangitis. (Assis, D. N., and Bowlus, C. L., 2023)Diagnostics Development of PSC
- Imaging Diagnostics
Imaging tests such as ultrasound, CT scan, MRI, ERCP, and MRCP can be used to diagnose PSC to show abnormalities in the bile ducts and liver.
- Gene Diagnostics
Fluorescence in situ hybridization (FISH) can be used as a means of evaluating PSC diseases to distinguish reactive/inflammatory processes from malignant tumors.
Therapy of PSC
Small Molecule Drug Therapy
Small molecule drug therapy is often used to treat PSC by targeting specific pathways involved in the inflammatory response and fibrosis development in the bile ducts. Drugs such as ursodeoxycholic acid (UDCA), obeticholic acid (OCA), and other farnesoid X receptor (FXR) agonists are commonly used to manage PSC symptoms and slow disease progression. Bexotegrast, as an inhibitor of integrin αVβ6 and αVβ1, has shown promise in blocking the activation of transforming growth factor β, which plays a crucial role in fibrosis development in the liver in conditions like PSC.
Immune Therapy
Because of the role of the immune system in PSC pathogenesis, HLA and non-HLA immune risk loci, and frequent recurrence post-transplantation, immunotherapy may also be employed to treat PSC. Drugs like infliximab, rituximab, and vedolizumab are used to target specific immune cells and pathways involved in PSC pathogenesis. Vidofludimus calcium as a dihydroorotate dehydrogenase inhibitor, induces apoptosis in proliferating lymphocytes and reduces the release of interleukin 17 and interferon-γ, and recently was shown to modestly reduce cholestatic liver tests in PSC.
Modulate the Gut Microbiome Therapy
Modulate the gut microbiome therapy is another emerging approach to treating PSC, as there is increasing evidence to suggest that dysbiosis (imbalanced microbiota) in the gut may contribute to the development and progression of the disease. Probiotics, prebiotics, and fecal microbiota transplantation (FMT) have shown promising results in restoring gut microbiota balance and improving symptoms in PSC individuals. In addition, taking antibiotics such as vancomycin can also effectively reduce liver enzyme levels and Mayo risk score.
Our Services
Our company has professional researchers in rare disease research and is equipped with advanced technologies that can expedite the journey toward effective therapies for conditions like PSC. It can provide services such as animal model construction and therapeutic platform development, and enhance individual outcomes in rare diseases towards personalized therapeutics.
Platforms of PSC Therapy Development
Animal Models of PSC
The animal models are valuable tools for studying the mechanisms underlying PSC and for testing new therapeutic strategies for this disease. We can offer you animal models of PSC that involve genetic alterations in specific genes or administration of compounds that cause liver inflammation, fibrosis, or bile duct injury.
| Chemical-induced Models | |
| These models inducing liver injury and inflammation through various chemical compounds, commonly Dextran Sulfate Sodium (DSS) or Alpha-Napthylisothiocyanate (ANIT) used to induce liver injury, bile duct injury, and fibrosis resembling features of PSC in animal models. | |
| Optional Models | DSS model, ANIT model |
| Genetically Engineered Models | |
| Animal models of PSC can be created through gene editing techniques tools like CRISPR/Cas9 to simulate the genetic mutations associated with the condition. These genetically engineered animal models can be valuable for studying the mechanisms underlying PSC, testing potential treatments, and identifying novel therapeutic targets. | |
| Optional Models | Mdr2/Abcb4-/- model |
| Mechanical-induced Models | |
| Bile duct ligation (BDL) is a surgical model in which the bile duct is surgically obstructed, leading to cholestasis, liver inflammation, fibrosis, and bile duct damage. BDL rats are used to study the pathophysiology of PSC and to test potential treatments. | |
| Optional Models | BDL model |
| Optional Species | Mice, Rats, Others |
Our company can offer bespoke services tailored to meet your specific research needs in the realm of PSC. From the inception of constructing animal models to the pharmacokinetics analysis and drug safety evaluation.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Assis, D. N., and Bowlus, C. L. "Recent Advances in the Management of Primary Sclerosing Cholangitis." Clinical gastroenterology and hepatology 21.8 (2023): 2065–2075.
- Trauner, M., et al. "Primary sclerosing cholangitis-Diagnosis and treatment 2024." Innere Medizin (Heidelberg, Germany) 65.4 (2024): 347–356.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.