Epigenomic Liquid Biopsy for Early Detection and Monitoring of Metabolic Dysfunction-Associated Steatohepatitis

Objectif

The silent epidemic of Metabolic dysfunction-associated steatohepatitis (MASH) has a massive toll on human health. MASH is characterized by fat accumulation in the liver, accompanied by inflammation and liver-cell injury. Closely linked to metabolic conditions such as Type 2 diabetes and Obesity, MASH has become one of the fastest-growing causes of chronic liver disease worldwide. Individuals remain asymptomatic for years while the disease gradually advances from fat accumulation to inflammation, fibrosis, and eventually to irreversible cirrhosis and hepatocellular carcinoma.

The recent development of multiple pharmaceutical interventions, two recently approved in the US and one in the EU, opens new opportunities to treat MASH and reverse the course of the disease. However, the majority of patients who stand to benefit from these treatments are undiagnosed. Current non-invasive solutions are not sufficiently accessible, and lack the specificity and sensitivity for relevant disease stages. Furthermore, non-invasive indicators of treatment success today are based on clearing of fibrosis, a slow process that can take months or years, and does not represent the full scope of the disease.

We have developed cfChIP-seq, a liquid biopsy that uses chromatin fragments in blood to analyze gene activity in the cells contributing to cell-free DNA. This technology is particularly relevant to liver diseases such as MASH, as it provides a high-resolution view of molecular changes in the liver and immune system during the course of the disease.

We plan to develop methods for accurate early diagnosis, staging, and monitoring of MASH. This effort will be supplemented by a multi-center cohort of patients to train and validate these tools. Together, these will establish a pre-clinical evaluation of the assay's capabilities for MASH diagnosis and monitoring, and enable the development of a product that would revolutionize MASH management and improve patients' lives.