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.

Abstract: Measurements in test tissue and drug-treated tissue can be used to determine an effect of the drug, e.g., on cardiomyocytes. Optical measurements of test tissue (e.g., including immature or animal CMs) can be complemented with observations of the extracellular potential, e.g., using multi electrode arrays (MEAs), as part of accurately estimating the current density of an ion channel, e.g., the sodium channels. The estimating of an ion current density (e.g., by inversion) of the ion (e.g., sodium) current can also use an observation of the conduction velocity, which can be computed using measurements of extracellular waves across electrodes. Example optical measurements can be of a transmembrane voltage (Vm) and intracellular calcium concentration (Cai). An example electrical measurement can be of an extracellular potential (U).

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.