Leveraging decades of specialized hepatobiliary research expertise, Ace Therapeutics offers tailored preclinical solutions for cholangitis from disease model development to novel drug optimization. All strategically designed to accelerate and de-risk drug development pipeline from target identification through preclinical studies.
Overview of Cholangitis
Cholangitis is an inflammatory condition of the bile ducts, commonly caused by bacterial infection due to biliary obstruction (e.g., gallstones, strictures, or tumors). The most prevalent causative pathogens, including E. coli and Klebsiella species, necessitate a comprehensive therapeutic approach targeting multiple pathological aspects of this complex hepatobiliary disorder.
Fig. 1 Pathogenesis of primary biliary cholangitis. (You H, et al., 2022)
We customize experimental models to meet specific research needs across a range of species from rodents to large animals, whether it is to study the complex molecular mechanisms of disease or to assess the efficacy of novel therapeutic candidates.
Animal Models for Primary Sclerosing Cholangitis (PSC)
- Genetic Manipulation
- Chemical Induction
Animal Models for Primary Biliary Cholangitis (PBC)
- Spontaneous Animal Models
- Induced Animal Models
Cholangitis Drug Development Services
Drug Target Identification and Validation Services
- Transcriptomics and Single-cell RNA Sequencing
Our integrated transcriptomic and single-cell RNA sequencing platform helps clients delineate dysregulated signaling networks in cholangitis pathogenesis, facilitating the discovery of novel molecular targets for intervention strategies.
- Metabolomics Analysis
Utilizing high-resolution metabolomic profiling, we quantify pathological alterations in bile acid composition characteristic of cholangitis progression, enabling data-driven development of targeted metabolic therapies.
- Microbiome Analysis
Capitalizing on associations between Enterobacteriaceae and cholangitis, we identify disease-specific dysbiosis patterns enabling rational development of novel microbiome modulators with enhanced biliary tract targeting capabilities.
Drug Screening and Discovery Services
- Drug Screening in Bile Duct Cell Models
We use primary human cholangiocytes (H69, NHC), which are induced by LPS and bile acids to produce key aspects of cholangitis pathology, thus allowing us to quantitatively assess the effects of drug candidates on inflammatory mediator production and epithelial barrier restoration.
- Drug Screening in Bacterial Infection Models
We employ standardized in vitro assays to assess compound efficacy against prevalent cholangitis pathogens through quantitative determination of minimum inhibitory concentrations (MIC) and bactericidal kinetics, providing critical data for anti-infective therapeutic development.
Preclinical Efficacy and Mechanism Study Services
- In Vitro Drug Biliary Efficacy Study
Our primary human biliary epithelial cell models enable rigorous preclinical efficacy evaluation of biliary protective compounds through quantitative evaluation of tight junction integrity (ZO-1/claudin-5 expression), inflammatory response modulation (IL-6/IL-8 secretion profiles), and epithelial barrier function (transepithelial electrical resistance).
- Bile Duct Inflammation Analysis
Through established cholangitis models (bile duct ligation and LPS perfusion), we perform rigorous, multi-parametric compound characterization integrating biochemical marker profiling, quantitative biliary inflammation scoring, and ductal injury assessment, effectively bridging preclinical drug efficacy data with clinically relevant therapeutic outcomes.
- Biliary Fibrosis Analysis
The Mdr2-/- genetic mouse model serves as a powerful tool for preclinical evaluation of therapeutic candidates, enabling quantitative evaluation of biliary fibrosis progression, ductular reaction, and hepatic functional preservation. This well-validated preclinical model provides robust efficacy data for primary sclerosing cholangitis drug development.
At Ace Therapeutics, our hepatobiliary disease specialists leverage deep expertise to design research solutions for clients' cholangitis program. If you would like to learn more about our services, please do not hesitate to contact us.
Reference
- You, H.; et al. APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int. 2022, 16(1):1-23.
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