Conatus Pharmaceuticals Announces Upcoming Oral Presentation at EASL Annual Meeting
Presentation #PS-004, “The gut-liver axis is essential for disease progression in the Mdr2−/− mouse model of primary sclerosing cholangitis,” will be delivered by lead author
The researchers noted that PSC, a disease affecting bile ducts in the liver which can lead to cirrhosis and liver failure, is strongly associated with inflammatory bowel disease, and that the gut-liver connection plays a critical role in PSC onset and progression. They investigated gut-liver interactions and inflammasome activation in the Mdr2−/− mouse model resembling PSC. Their results showed that inflammation in the Mdr2−/− mouse model showed characteristic increases in apoptotic cell death, progressive bile duct proliferation and periportal fibrosis development. The bile acid composition was abnormal and reflective of changes in intestinal bacteria.
Conatus’ pan-caspase inhibitor IDN-7314 was administered as a treatment to block caspase activation, resulting in reduced inflammasome activation and demonstrated beneficial effects on liver injury, periportal inflammation, serum bile acid profile as well as imbalance in the intestinal bacteria. The researchers confirmed the importance of the gut-liver connection in the Mdr2−/− mouse model of PSC, and concluded that blockage of bile ducts triggers an intestinal bacteria imbalance and migration of bacteria and related toxins to the portal vein of the liver, followed by increased inflammation and liver injury. They further concluded that this cascade of events can be blocked by pan-caspase inhibition.
“The confirmation of the links between liver and gut implications in PSC suggest that treatments addressing the underlying mechanisms may provide benefits in both organ systems,” said
IDN-7314 is an orally active pan-caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death (or apoptosis), which has demonstrated reduction of relevant biomarkers in two preclinical models of PSC. The Mdr2-/- mouse model is considered the current benchmark nonclinical model of PSC. IDN-7314 also reduced biochemical markers in a new acute preclinical model of PSC. These results suggest the involvement of caspases in the progression of PSC. IDN-7314 was granted Orphan Drug Designation for the treatment of PSC by the
Conatus is a biotechnology company focused on the development of novel medicines to treat liver disease. In collaboration with
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding: the potential for IDN-7314 as a treatment for PSC; and caspase inhibitors’ potential to interrupt the progression of a variety of diseases. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: the risk that the preclinical results may not be predictive of future clinical results; Conatus’ ability to utilize the
Source: Conatus Pharmaceuticals Inc.