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Non-​Clinical

Aramchol signif­i­cantly down regulates the three key pathologies of NASH: Steatosis, Inflammation and Fibrosis in multiple animal models.

Aramchol significantly reduces liver steatosis & inflammation in MCD diet model
▷ Methionine and Choline Deficient (MCD) diet induces amino­trans­ferase elevation and changes in hepatic histo­logical features charac­terized by steatosis, local inflam­mation, hepatocyte necrosis and fibrosis.
▷ The MCD is deficient in two essential factors for the synthesis of phosphatidyl­choline, which is involved in VLDL production and secretion from the liver.
▷ The MCD is one of the most commonly used animal models of NASH, as it induces a liver pathology that resembles the sequence and progression of liver pathology seen in humans.
Delire, B., Stärkel, P., & Leclercq, I. (2015). Animal models for fibrotic liver diseases: what we have, what we need, and what is under devel­opment. Journal of Clinical and Translational Hepatology, 3(1), 53.

Illustration
Illustration

Iruarrizaga‐Lejarreta, Marta, et al. “Role of Aramchol in steato­hep­atitis and fibrosis in mice.” Hepatology Communications 1.9 (2017): 911–927.

Aramchol significantly down regulates/​normalized liver fibrosis in MCD diet model

Iruarrizaga‐Lejarreta, Marta, et al. “Role of Aramchol in steato­hep­atitis and fibrosis in mice.” Hepatology Communications 1.9 (2017): 911–927.

Aramchol significantly reduces liver fibrosis in TAA model
▷ Thioacetamide (TAA) is the most commonly used toxic agent to induce liver fibrosis.
▷ Repeated IP injec­tions of TAA leads to severe fibrosis /​cirrhosis.
▷ Of all models for fibrosis, the TAA model shares multiple charac­ter­istics with human liver fibrosis and is considered to best predict efficacy in humans.
Delire, B., Stärkel, P., & Leclercq, I. (2015). Animal models for fibrotic liver diseases: what we have, what we need, and what is under devel­opment. Journal of Clinical and Translational Hepatology, 3(1), 53.

Aramchol™ Significantly Reduces Liver Fibrosis In TAA Model
Illustration Of Liver

R. Golan-​Gerstl1, M. Valitsky1, R. Oren1, E. Brazovski2, L. Hayardeny1, S. Shimon Reif. “The anti-​fibrotic effect of aramchol on liver fibrosis in TAA animal model” (2017); The inter­na­tional liver congress (EASL), Amsterdam, the Netherlands.

Aramchol down regulates stellate cell proliferation and collagen production
▷ The human hepatic cell line LX-​2 has been described as tool to study mecha­nisms of hepatic fibro­ge­nesis and the testing of antifi­brotic compounds.
▷ The human HSC cell lines Lieming Xu-​1 (LX-​1) and Lieming Xu-​2 (LX-​2) were origi­nally generated by trans­for­mation of cultured primary HSC obtained from a male human liver with a plasmid encoding the SV40 large T-​antigen expressed under the control of a Rous sarcoma virus promoter (LX-​1) or by sponta­neous immor­tal­ization of a subset of early passaged LX-​1 cells that were grown in low serum condi­tions (LX-​2).
Weiskirchen, Ralf, et al. “Genetic charac­ter­istics of the human hepatic stellate cell line LX-​2.” PloS one 8.10 (2013): e75692

Aramchol™ Down Regulates Stellate Cell Proliferation And Collagen Production

Iruarrizaga‐Lejarreta, Marta, et al. “Role of aramchol in steato­hep­atitis and fibrosis in mice. “Hepatology Communications 1.9 (2017): 911–927.

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