Patent ID: 8318488

Claim:
An in vitro method for screening and identifying a candidate substance capable of ameliorating hypertrophic cardiomyopathy comprising: (a) differentiating a pluripotent stem cell to a cardiomyocyte in vitro; (b) inducing the cardiomyocyte to display a first cardiac hypertrophic phenotype; (i) wherein the inducing results in the cardiomyocyte having an increased size, protein production and/or sarcomeric assembly relative to the same cardiomyocyte prior to the inducing in step (b); and/or (ii) wherein the inducing results in the cardiomyocyte expressing atrial natriuretic factor (ANF) and/or brain natriuretic protein (BNP) genes or their products in an amount greater than the cardiomyocyte prior to the inducing in step (b); (c) contacting a test sample comprising the in vitro differentiated cardiomyocyte with a substance to be tested prior, during or after said cardiomyocyte is induced to display the cardiac hypertrophic phenotype; (d) measuring a second cardiac hypertrophic phenotype in the cardiomyocyte of step (c); (e) comparing the measurement obtained in step (d) to that of a cardiomyocyte not subjected to the substance to be tested; wherein the candidate substance is identified on the basis of whether the measurement of the second cardiac hypertrophic phenotype in the cardiomyocyte of step (d) is consistent with a reduction in hypertrophic cardiomyopathy.