TITLE: New Diagnostic Test for Drug Induced Liver Injury and Chronic Hepatitis C
CASE NUMBER: C10654
UNMET NEED
Idiosyncratic drug-induced acute liver failure (Id-ALF) is the third most common cause of acute liver failure in the United States and is the leading cause for drug removal from the market. A type of Id-ALF develops in susceptible individuals following administration of halogenated volatile anesthetics. Autoantibodies to human cytochrome P4502E1 (CYP2E1) are found in persons with Id-ALF from anesthetics and in persons exposed to halogenated volatile anesthetics without Id-ALF. CYP2E1 autoantibodies in exposed persons are of an immunoglobulin subclass distinct from patients with anesthetic-induced ALF, which may suggest that immune reactions to distinct portions, or epitopes, of the CYP2E1 protein may have a role in the presence or absence of Id-ALF. Yet, the immunogenic CYP2E1 epitopes responsible for CYP2E1 autoantibodies in patients with anesthetic Id-ALF have not previously been identified.
TECHNICAL DESCRIPTION
JHU researchers have developed a diagnostic test to screen for individuals at risk of developing Idiosyncratic drug-induced acute liver failure (Id-ALF), which occurs in individuals following administration of halogenated volatile anesthetics. Halogenated volatile anesthetics bind to and alter native liver proteins with reactive products of their metabolism thus creating novel autoantigens capable of eliciting allergic or autoimmune responses. Critical epitopes responsible for autoantibody production in patients with anesthetic Id-ALF have been identified using human sera from anesthetic hepatitis patients. Using these identified epitopes, a diagnostic test has been developed for drug induced acute liver failure. Advantages include:
1. Diagnostic test can become a standard vulnerability test for patients about to embark on a course involving potentially toxic drugs.
2. Test has been used at JHU and has shown efficacy in several patient populations.
3. Technology can also be used to design therapeutic intervention strategies for susceptible patients prior to exposure to potentially triggering drugs or viruses.
MAJOR RESULTS
The invention is at the Discovery phase. These epitopes can be used to develop
- drug screening assays.
- preclinical toxicology markers/assays.
DISEASE INDICATION
Liver Diseases
ASSOCIATED PUBLICATIONS
None at This Time
TECHNOLOGY CLASSIFICATION
Primary Category: Diagnostics
Primary Subcategory: Research Tools
ASSOCIATED REPORTS OF INVENTION (ROIs) AND INTELLECTUAL PROPERTY (IP) FILING NUMBERS
ROI #: C10654
TITLE: Recognition of cyp2e1 Epitopes
STATUS: US Patent Pending
PRIORITY DATE: 2/26/2009
IP FILING NUMBERS: US 20120040377 A1
