Abstract: A process is provided for using a model to identify potential combinations of drugs to repair an action potential. A model is created for the normal state of an action potential along with a model for an abnormal state that reflects the effect of a disease or mutation on the action potential. Using a known action potential, a treated state can be generated that represents the abnormal state modified by one or more drug effects. By optimizing a formulation for a drug combination to minimize the differences between the treated state model and the normal state model, a combination of drug therapies that can potentially repair an action potential can be identified.
Abstract: The present invention provides a method for determining the effect of a drug on a mature cardiomyocyte. In some embodiments, the method comprises using transmembrane voltage and/or intracellular calcium data obtained from control immature cardiomyocytes and those that have been contacted with the drug to parameterize models of immature cardiomyocytes, then applying a maturation matrix to generate a mature cardiomyocyte model. The method is useful for, among other things, predicting whether a drug may have proarrhythmic properties and for determining whether a particular drug should be administered to a patient.
Type:
Application
Filed:
February 1, 2019
Publication date:
August 8, 2019
Applicant:
Simula Innovation
Inventors:
Aslak Tveito, Samuel Wall, Karoline Horgmo Jaeger