Two Compartment Model for Detecting the Toxicity of Liver Metabolites

Overview

Liver toxicity is a significant reason many new drugs fail in clinical trials. Primary human hepatocytes (PHHs) are the current gold standard for in vitro liver models; however, they have a number of limitations. We have invented an easy-to-use two-compartment device that provides in vitro 3D high-throughput prediction for safety assessments through the liver-metabolizing capability of its microtissue plates.

Market Opportunity

The liver is the major organ that contributes to the metabolism of biomolecules, including drugs and chemicals. Often, new drugs and chemicals are not toxic until the liver metabolizes them, converting them into toxic metabolites. Primary human hepatocytes (PHHs) have a number of limitations, including donor-specific variability, a finite number of donors, and rapid loss of hepatocyte functionality in vitro. Thus, there is a need for simple 3D microtissues that can be rapidly tested for pathology in vitro using molecular and functional endpoints to identify adverse effects.

Innovation and Meaningful Advantages

Our invention provides an in vitro 3D high-throughput prediction for safety assessments, through the liver-metabolizing capability of its microtissue plates. The two-compartment device contains 3D metabolizing and hormone-producing microtissues in the first compartment and a selected target cell in the second compartment, with a permeable wall between the compartments. When a test compound is added to the first compartment, it is metabolized. The metabolites then freely and passively diffuse between the compartments through the permeable wall, mediating an effect on the target microtissue. In this way, the device screens for toxic metabolites. Discovery scientists can rapidly select lead compounds with desirable metabolic profiles, while safety scientists can determine the safety of drugs, pesticides, and environmental chemicals.

Collaboration Opportunity

We are interested in exploring 1) research collaborations with leading research companies; and 2) licensing opportunities with companies.

Principal Investigator

Kim Boekelheide, MD, PhD
Professor of Pathology and Laboratory Medicine (Research)
Brown University

IP Information

US Utility 2022/0081659A1, Issued March 17, 2022

 

Contact

Melissa Simon, PhD
Director of Business Development
melissa_j_simon@brown.edu
Brown Tech ID 2578
Patent Information: