We totally support the development of anti-NASH drugs from target validation to evaluation in animal models!
Despite the increasing number of patients with non-alcoholic steatohepatitis (NASH) worldwide, there is no effective treatment. A multilateral approach, such as elucidation of the etiology and disease progression, selection of promising compounds, and establishment of useful biomarkers, etc., is required for the development of anti-NASH drugs. Axcelead Drug Discovery Partners (hereinafter referred to as Axcelead DDP) provides appropriate solutions by utilizing abundant assay systems and various NASH models.
- Step 1. Target identification and validation (e.g., KO/Tg mice)
- Step 2. High-throughput screening
- Step 3. Antifibrotic evaluation in a co-culture system of hepatocyte + hepatic stellate cell
- Step 4-1. Drug efficacy evaluation in various NASH models
- Step 4-2. Histopathological evaluation
- Step 4-3. Evaluation of inflammatory responses
Step 1. Target identification and validation (e.g., KO/Tg mice)
- Identify target molecules with comprehensive gene expression analysis using samples from patients and disease model
- Validate anti-NASH effects of commercially available inhibitors/activators/antibodies for the target molecules in NASH models
- Confirm ameliorative/detrimental effects on hepatic steatosis and fibrosis in target molecule-KO mice
Step 2. High-throughput screening
- We provide high-quality hit compounds for a wide range of targets using the largest industrial class, high-quality compound libraries, and a variety of high-throughput screening techniques.
Step 3. Cellular assay
Antifibrotic evaluation in a co-culture system of hepatocyte + hepatic stellate cell
- We can perform cellular assays in an environment close to that of NASH patients using the co-culture system of human hepatocyte + hepatic stellate cell.
In the early stages of drug development, candidate compounds for in vivo experiments are selected by a cellular assay mimicking NASH patients.
Step 4. Evaluation in NASH model
(e.g., PK/PD assay, drug efficacy)
Step 4-1. Drug efficacy evaluation in various NASH model
- We can propose the best in vivo model and parameters for your needs and targets from our various NASH models and assay systems.
- We can select compounds for evaluation in NASH models by cellular assay and PK/PD studies.
Multilateral evaluation in the best NASH models for your target molecule contributes to increasing the success rates of clinical trials.
Step 4-2. Histopathological evaluation
- Certified pathologists (JSTP/JCVP*1) with comprehensive experience support the evaluation, including scoring for steatosis and inflammation (similar to NAS*2).
- Fibrosis area measurement with Sirius red staining sections and image analysis with immunohistochemistry for target molecules are also available.
*1 JSTP: Japanese Society of Toxicologic Pathology, JCVP: Japanese Collage of Veterinary Pathologists
*2 NAS: NAFLD Activity Score (used widely for diagnosis or as a measure for therapeutic response)
With one-stop service ranging from blood parameter measurement to pathological evalulation, we can quickly deliver the data necessary for drug efficacy determination and contribute to rapid drug discovery research.
Step 4-3. Evaluation of inflammatory response
- We can perform detailed immunophenotyping of cells in a small amount of blood and various tissues including lymphoid organs using a 5-laser-equipped flow cytometer.
- The MultiPlex analysis system allows us to evaluate the production of various biomarkers, such as cytokines, and drug efficacy on the response.