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.
HTS（High-Throughput Screening）
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.
With abundant experience and knowledge, we provide appropriate solutions for drug efficacy evaluation, MOA analysis and new target identification on inflammatory and immune responses in NASH
