Targeting the gut biome to treat persons with alcohol-associated hepatitis
Targeting the gut biome to treat persons with alcohol-associated hepatitis
Our Scientific Focus
Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality and is currently the leading cause for liver transplantation in the United States. Alcohol-associated hepatitis is a severe and life-threatening form of liver disease. Our team has identified cytolysin—an exotoxin that is secreted specifically by Enterococcus faecalis (E. faecalis)—as a cause of hepatocyte death and liver injury. We have discovered that patients with alcohol-associated hepatitis have increased numbers of E. faecalis in the gut microbiome with the presence of cytolysin-positive E. faecalis correlated with the severity of liver disease and with mortality in patients with alcohol-associated hepatitis. We believe that a reduction in cytolysin producing E. faecalis in the gut may result in significant liver disease improvement. Our first therapeutic product, NTR-101, is a product composed of three to four bacteriophages that will be clinically developed to treat these patients.
Preclinical experiments in humanized mice colonized with bacteria from the faeces of patients with alcohol-associated hepatitis showed the therapeutic effects of our bacteriophages targeting cytolytic E. faecalis. Our selected bacteriophages decreased cytolysin in the liver by specifically targeting cytolytic E. faecalis and abolished ethanol-induced liver disease in the animals, which provides a method for precisely editing the intestinal microbiota (Duan et al, 2019 ). Nterica Bio will run clinical trials to validate the relevance of its preclinical findings, and to confirm whether this therapeutic approach is effective for patients with alcohol-associated hepatitis.
Link to PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872939/pdf/nihms-1540838.pdf
Link to Nature (pay for access) https://www.nature.com/articles/s41586-019-1742-x
Meet the Team
Bernd Schnabl, MD
Sandra Morales, PhD
Sandra Morales, PhD
Bernd Schnabl, MD is a Professor of Medicine and Director of the San Diego Digestive Diseases Research Center. He is a board certified Physician-scientist at UCSD Medical Center & the VA Hospital San Diego. He is the Founder of Nterica.
Sandra Morales, PhD
Sandra Morales, PhD
Sandra Morales, PhD
Sandra Morales is a microbiologist with specific doctoral expertise in molecular biotechnology and bacteriophage science. She has over 17 years of industrial experience developing bacteriophage-based products against a variety of pathogens, with an emphasis on clinical and manufacturing development.
Anita Busquets, MBA
Sandra Morales, PhD
Anita Busquets, MBA
Anita Busquets is a financial biotech executive. She brings over 35 years of executive operational and financial experience as a CFO, raising capital and growing startups to successful exits.