NASH is a progressive disease culminating in associated morbidity and mortality. This pathology takes years to manifest itself in the clinic and progresses through multiple stages starting from steatosis (fatty liver) to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. The etiology of NASH is multifactorial in nature, comprising both genetic and environmental factors.
Currently, patients in the advanced stages have few therapeutic options and organ transplant is often the only means for survival. However, this is also fraught with risks, costs and quality of life issues. It is also challenging to be able to diagnose and identify those patients in whom the pathology is likely to progress to this stage. An unavailability of clinically validated markers that can help identify the underlying pathology and therefore enable the selection of the appropriate treatment regimen remains a gap in the current diagnosis and treatment paradigm for NAFLD.
Fibrosis: a critical pathology in NASH
While Metabolic Stress and Inflammation are the main exogenous triggers for chronic pathology in the liver, Fibrosis is the critical pathological process that mediates the progression into later stages of disease. We have therefore focused on Fibrosis as a key stage in the progression of pathology across multiple cell types within the liver. Our integrative Network Biology Approach has helped us generate the understanding of NASH at the molecular level and identify novel therapeutic mechanisms identified the critical molecular mechanisms in Fibrosis across cell types that drive the transformation of functional cells into myofibroblasts and fibrotic tissue across different cell types within the liver.
Connexios has also identified and qualified several novel targets that can modulate these mechanisms to halt or delay the transformation of functional cells to fibrotic tissue. These targets have been rigorously assessed in vitro and in proprietary animal models of Liver disease created at Connexios.
By impacting the core molecular mechanisms driving fibrosis, these targets also offer great promise in other diseases that are mediated and characterized by fibrosis including Chronic Kidney Disease and Lung Fibrosis.
Novel targets for developing anti-fibrotic agents
Potential Clinical Benefit
CNX-014: Stress Kinase
Lipid messenger Signaling
ECM Derived Signaling
ECM derived Signaling
CNX-025: Tyrosine KinaseReceptor
- Detailed target biology and anti-fibrotic mechanism has been generated using in silico system.
- Extensive in-vitro studies for initial proof of concept, using either over-expression or knockdown methods in our proprietary liver slice model and other cell systems under fibrosis related condition
|Novel anti-fibrotic agents that directly targets the fibrotic mechanisms thereby delays or protects from the worsening of various chronic fibrotic diseases and associated complications. Provides an efficient handle for pre-transplantation management.