STAM mouse | Adiponectin-derived peptide study to inhibit MASH and fibrosis progression
Today, we would like to introduce an example of a proof-of-concept study of adiponectin-derived peptide ALY688 in STAMTM mice, which was published in Clinical and Translational Science by a research team from Allysta Pharmaceuticals, Inc. in the United States.
The adiponectin – derived peptide ALY688 protects against the development of metabolic dysfunction-associated steatohepatitis – Huang – 2024 – Clinical and Translational Science – Wiley Online Library
(Zhe Huang et al., Clinical and Translational Science, 17, e13760, 2024) PMID: 38847320
Group design; 5 groups: Subject group (Vehicle), ALY688 low-dose group (subcutaneous), ALY688 high-dose group (subcutaneous), ALY688 low-dose group (osmotic pump), ALY688 high-dose group (osmotic pump)
Endpoint; serum ALT, serum AST, HE staining and NAFLD Activity score
In this paper, a pharmacodynamics evaluation study of ALY688 using STAMTM mice as well as CDAHFD model mice has been conducted. Based on the data obtained from these studies, they report on the anti-NASH and anti-fibrosis effects of ALY688.
Several ideal MASH (NASH) models have been described in the literature, but currently no model exists that meets all of these criteria, and it is recommended that at least two or more MASH models be used in drug efficacy evaluation studies (Daniel Jahn et al , Biochim Biophys Acta Mol Basis Dis., 1865, 943-953, 2019, Prasanna K. Santhekadur et al, J Hepatol., 68, 230-237, 2019, Henrik H Hansen et al, Drug Discov Today, 22, 1707-1718, 2017).
Below you find a table, comparing STAMTM and CDAHFD mice:
Table 1. Comparison between STAMTM mice and CDAHFD
STAMTM mice show MASH, fibrosis, and hepatocellular carcinoma with a background of type 2 diabetes, a pathological progression similar to human MASH pathology, but fibrosis does not progress to cirrhosis. On the other hand, the CDAHFD model does not have a background of metabolic abnormalities but shows severe fibrosis. By conducting drug efficacy evaluation studies using both models, the shortcomings of both models can be complemented and the full potential of the test substance for treating the MASH pathology can be evaluated.
Apart from STAMTM and CDAHFD mice, we also have background data for other disease models such as GAN diet, HFHF, MCD, and WD +CCl4, and can suggest the best fitting MASH model based on your study objectives.