Nonalcoholic steatohepatitis (NASH), as a more aggressive type of nonalcoholic fatty liver disease (NAFLD), has affected millions of people in the US, becoming one of the most common chronic liver diseases in the western world. Some NASH patients could develop into cirrhosis or cancer. However, no medications for the treatment of NASH have been approved by the FDA except for a liver transplant, which forces a great number of researchers to get dedicated to the development of NASH therapies as well as the diagnosis of this disease.
This post discusses the challenges and recent updates on the NASH drug discovery and its biomarker development.
Biomarkers for NASH Diagnosis
A recently published report assesses that the NASH biomarkers treatment market will show exponential growth and reach USD 1960.4 million by 2024. The surging need for NASH biomarkers gets enhanced by the increasing prevalence of NASH and growing demand for non-invasive diagnostic tests. Though researchers have identified that the characteristics of nonalcoholic steatohepatitis include liver inflammation and damage caused by a buildup of fat in the liver, it’s not enough to predict and diagnose NASH. Currently, a liver biopsy takes the dominant role in making a definitive diagnosis. However, liver biopsy in NAFLD/NASH patients also appears an increasing risk for liver-related morbidity and mortality, which highlights the necessity of assessing liver damage through non-invasive surrogate markers.
Biomarkers, as diagnostic tools for NASH, help predict disease progression and identify patients’ responses to a developed therapy. The market of NASH biomarkers can be classified into serum biomarkers, hepatic fibrosis biomarkers, apoptosis biomarkers, oxidative stress biomarkers, and others.
Drug Discovery for NASH
In the end stage of NASH, scar tissue and regenerative nodules resulting from the inflammation and fibrosis of NASH will replace the healthy liver tissue and damage normal functions of the liver. Due to the lack of approved NASH drugs while the growing numbers of NASH patients and associated liver transplantations, scientists have long devoted themselves to identifying novel drug therapies. For instance, the Cambridge Healthtech Institute’s 3rd Annual held on September 29 – 30, 2021 concentrated on NASH and fibrosis, discussing drug discovery for scarring of the liver, lung, and other organs, which advances the drug discovery for NASH treatment in some ways. Live science companies have also been dedicated to providing support from different aspects, such as potential biomarkers development services for NASH non-invasive diagnosis, potential therapeutic target development services, and in vivo or in vitro NASH-related preclinical model building services.
Challenges for NASH Drug Discovery
There is no confirmed pathogenesis of NASH but some assumptions have been widely accepted, including the two-hit hypothesis caused by both steatosis and inflammation, hepatocyte damage, and fibrosis, as well as the multiple parallel hits hypothesis caused by numerous conditions and factors in parallel.
Either of them describes the complexity of NASH, involving steatosis, inflammation, fibrosis, hepatocyte damage, final cirrhosis and hepatocarcinoma, and more. Staged disease processes ranging in a large time span bring great challenges for researchers when capturing useful information in an animal model in drug discovery. Most of the time, scientists have to build multiple animal models covering different aspects of NASH, for instance, one animal model for anti-steatosis and while anti-fibrosis in another, and then conclude their understanding of drug candidates. Other factors like the translatability of models and relative lack of patients with biopsy-confirmed NASH also make NSAH drug discovery a challenging task.