Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays

Toxicological Sciences

Volumn 134, Issue 2, 2013, Pages 412-426

  Harris, Kate ^a   Aylott, Mike ^b   Cui, Yi ^a   Louttit, James B ^a   McMahon, Nicholas C ^a   Sridhar, Arun ^a  

^a Safety Assessment   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Cardiovascular safety; Electrophysiology: ion channel blockers; hiPSC CM; Multielectrode array; Preclinical

Indexed keywords

1 [2 (6 METHYL 2 PYRIDYL)ETHYL] 4 (4 METHYLSULFONYLAMINOBENZOYL)PIPERIDINE; CISAPRIDE; FLECAINIDE; GSK A COMPOUND; GSK B COMPOUND; ION TRANSPORT AFFECTING AGENT; MEXILETINE; NIFEDIPINE; QUINIDINE; TERFENADINE; UNCLASSIFIED DRUG; VERAPAMIL;

ANTIARRHYTHMIC ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG SAFETY; ELECTROCARDIOGRAM; HEART ARRHYTHMIA; HEART DEPOLARIZATION; HEART ELECTROPHYSIOLOGY; HEART MUSCLE CELL; HEART REPOLARIZATION; HUMAN; HUMAN CELL; IC 50; PLURIPOTENT STEM CELL; RISK ASSESSMENT; SODIUM CURRENT;

CARDIOVASCULAR SAFETY; ELECTROPHYSIOLOGY: ION CHANNEL BLOCKERS; HIPSC-CM; MULTIELECTRODE ARRAY; PRECLINICAL.;

CALCIUM CHANNEL BLOCKERS; CELLS, CULTURED; HUMANS; MYOCYTES, CARDIAC; PLURIPOTENT STEM CELLS;

EID: 84880678710     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kft113     Document Type: Article

References (50)

1. Ando, K., Hombo, T., Kanno, A., Ikeda, H., Imaizumi, M., Shimizu, N., Sakamoto, K., Kitani, S., Yamamoto, Y., Hizume, S., et al. (2005). QT PRODACT: In vivo QT assay with a conscious monkey for assessment of the potential for drug-induced QT interval prolongation. J. Pharmacol. Sci. 99, 487-500.
2. Anson, B. D., Kolaja, K. L., and Kamp, T. J. (2011). Opportunities for use of human iPS cells in predictive toxicology. Clin. Pharmacol. Ther. 89, 754-758.
3. Baker, B. J., Gammill, J., Massengill, J., Schubert, E., Karin, A., and Doherty, J. E. (1983). Concurrent use of quinidine and disopyramide: Evaluation of serum concentrations and electrocardiographic effects. Am. Heart J. 105, 12-15.
4. Batey, A. J., and Doe, C. P. (2002). A method for QT correction based on beatto- beat analysis of the QT/RR interval relationship in conscious telemetred beagle dogs. J. Pharmacol. Toxicol. Methods 48, 11-19.
5. Campbell, T. J., Wyse, K. R., and Hemsworth, P. D. (1991a). Effects of hyperkalemia, acidosis, and hypoxia on the depression of maximum rate of depolarization by class I antiarrhythmic drugs in guinea pig myocardium: Differential actions of class Ib and Ic agents. J. Cardiovasc. Pharmacol. 18, 51-59.
6. Campbell, T. J., Wyse, K. R., and Pallandi, R. (1991b). Differential effects on action potential duration of class IA, B and C antiarrhythmic drugs: Modulation by stimulation rate and extracellular K+ concentration. Clin. Exp. Pharmacol. Physiol. 18, 533-541.
7. Cavero, I., Mestre, M., Guillon, J. M., Heuillet, E., and Roach, A. G. (1999). Preclinical in vitro cardiac electrophysiology: A method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 21(Suppl. 1), 19-31.
8. Duff, H. J., Wyse, D. G., Manyari, D., and Mitchell, L. B. (1985). Intravenous quinidine: Relations among concentration, tachyarrhythmia suppression and electrophysiologic actions with inducible sustained ventricular tachycardia. Am. J. Cardiol. 55, 92-97.
9. Ewart, L., Gallacher, D. J., Gintant, G., Guillon, J. M., Leishman, D., Levesque, P., McMahon, N., Mylecraine, L., Sanders, M., Suter, W., et al. (2012). How do the top 12 pharmaceutical companies operate safety pharmacology? J. Pharmacol. Toxicol. Methods 66, 66-70.
10. FDA. (2010). Pharmacology review of NDA 21-879. 18-19. FDA. Fish, J. M., and Antzelevitch, C. (2003). Cellular and ionic basis for the sex-related difference in the manifestation of the Brugada syndrome and progressive conduction disease phenotypes. J. Electrocardiol. 36(Suppl), 173-179.
11. FDA. Fish, J. M., and Antzelevitch, C. (2003). Cellular and ionic basis for the sex-related difference in the manifestation of the Brugada syndrome and progressive conduction disease phenotypes. J. Electrocardiol. 36(Suppl), 173-179.
12. Guo, L., Abrams, R. M., Babiarz, J. E., Cohen, J. D., Kameoka, S., Sanders, M. J., Chiao, E., and Kolaja, K. L. (2011a). Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Sci. 123, 281-289.
13. Guo, L., Qian, J. Y., Abrams, R., Tang, H. M., Weiser, T., Sanders, M. J., and Kolaja, K. L. (2011b). The electrophysiological effects of cardiac glycosides in human iPSC-derived cardiomyocytes and in guinea pig isolated hearts. Cell. Physiol. Biochem. 27, 453-462.
14. Halbach, M., Egert, U., Hescheler, J., and Banach, K. (2003). Estimation of action potential changes from field potential recordings in multicellular mouse cardiac myocyte cultures. Cell. Physiol. Biochem. 13, 271-284.
15. Hanson, L. A., Bass, A. S., Gintant, G., Mittelstadt, S., Rampe, D., and Thomas, K. (2006). ILSI-HESI cardiovascular safety subcommittee initiative: Evaluation of three non-clinical models of QT prolongation. J. Pharmacol. Toxicol. Methods 54, 116-129.
16. Harmer, A. R., Valentin, J. P., and Pollard, C. E. (2011). On the relationship between block of the cardiac Na+ channel and drug-induced prolongation of the QRS complex. Br. J. Pharmacol. 164, 260-273.
17. Heath, B. M., Cui, Y., Worton, S., Lawton, B., Ward, G., Ballini, E., Doe, C. P., Ellis, C., Patel, B. A., and McMahon, N. C. (2011). Translation of flecainideand mexiletine-induced cardiac sodium channel inhibition and ventricular conduction slowing from nonclinical models to clinical. J. Pharmacol. Toxicol. Methods 63, 258-268.
18. Himmel, H. M., Bussek, A., Hoffmann, M., Beckmann, R., Lohmann, H., Schmidt, M., and Wettwer, E. (2012). Field and action potential recordings in heart slices: Correlation with established in vitro and in vivo models. Br. J. Pharmacol. 166, 276-296.
19. Hondeghem, L. M., Dujardin, K., Hoffmann, P., Dumotier, B., and De Clerck, F. (2011). Drug-induced QTC prolongation dangerously underestimates proarrhythmic potential: lessons from terfenadine. J. Cardiovasc. Pharmacol. 57, 589-597.
20. Kamp, T. J., and Lyons, G. E. (2009). On the road to iPS cell cardiovascular applications. Circ. Res. 105, 617-619.
21. Kola, I., and Landis, J. (2004). Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov. 3, 711-715.
22. Kraushaar, U., Meyer, T., Hess, D., Gepstein, L., Mummery, C. L., Braam, S. R., and Guenther, E. (2012). Cardiac safety pharmacology: From human ether-a-gogo related gene channel block towards induced pluripotent stem cell based disease models. Expert Opin. Drug Saf. 11, 285-298.
23. Lawrence, C. L., Bridgland-Taylor, M. H., Pollard, C. E., Hammond, T. G., and Valentin, J. P. (2006). A rabbit Langendorff heart proarrhythmia model: predictive value for clinical identification of Torsades de Pointes. Br. J. Pharmacol. 149, 845-860.
24. Liu, T., Brown, B. S., Wu, Y., Antzelevitch, C., Kowey, P. R., and Yan, G. X. (2006). Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias. Heart Rhythm 3, 948-956.
25. Liu, T., Traebert, M., Ju, H., Suter, W., Guo, D., Hoffmann, P., Kowey, P. R., and Yan, G. X. (2012). Differentiating electrophysiological effects and cardiac safety of drugs based on the electrocardiogram: A blinded validation. Heart Rhythm 9, 1706-1715.
26. Lu, H. R., Hermans, A. N., and Gallacher, D. J. (2012). Does terfenadineinduced ventricular tachycardia/fibrillation directly relate to its QT prolongation and Torsades de Pointes? Br. J. Pharmacol. 166, 1490-1502.
27. Lue, W. M., and Boyden, P. A. (1992). Abnormal electrical properties of myocytes from chronically infarcted canine heart. Alterations in Vmax and the transient outward current. Circulation 85, 1175-1188.
28. Ma, J., Guo, L., Fiene, S. J., Anson, B. D., Thomson, J. A., Kamp, T. J., Kolaja, K. L., Swanson, B. J., and January, C. T. (2011). High purity human-induced pluripotent stem cell-derived cardiomyocytes: Electrophysiological properties of action potentials and ionic currents. Am. J. Physiol. Heart Circ. Physiol. 301, H2006-H2017.
29. Maltsev, V. A., Kyle, J. W., and Undrovinas, A. (2009). Late Na+ current produced by human cardiac Na+ channel isoform Nav1.5 is modulated by its beta1 subunit. J. Physiol. Sci. 59, 217-225.
30. Maltsev, V. A., Sabbah, H. N., Higgins, R. S., Silverman, N., Lesch, M., and Undrovinas, A. I. (1998). Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation 98, 2545-2552.
31. Maltsev, V. A., and Undrovinas, A. I. (2006). A multi-modal composition of the late Na+ current in human ventricular cardiomyocytes. Cardiovasc. Res. 69, 116-127.
32. Masumiya, H., Saito, M., Ito, M., Matsuda, T., Noguchi, K., Iida-Tanaka, N., Tanaka, H., and Shigenobu, K. (2004). Lack of action potential-prolonging effect of terfenadine on rabbit myocardial tissue preparations. Biol. Pharm. Bull. 27, 131-135.
33. Mirams, G. R., Cui, Y., Sher, A., Fink, M., Cooper, J., Heath, B. M., McMahon, N. C., Gavaghan, D. J., and Noble, D. (2011). Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk. Cardiovasc. Res. 91, 53-61.
34. Miyazaki, H., Watanabe, H., Kitayama, T., Nishida, M., Nishi, Y., Sekiya, K., Suganami, H., and Yamamoto, K. (2005). QT PRODACT: Sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. J. Pharmacol. Sci. 99, 523-529.
35. Muller, P. Y., and Milton, M. N. (2012). The determination and interpretation of the therapeutic index in drug development. Nat. Rev. Drug Discov. 11, 751-761.
36. Omata, T., Kasai, C., Hashimoto, M., Hombo, T., and Yamamoto, K. (2005). QT PRODACT: Comparison of non-clinical studies for drug-induced delay in ventricular repolarization and their role in safety evaluation in humans. J. Pharmacol. Sci. 99, 531-541.
37. Peng, S., Lacerda, A. E., Kirsch, G. E., Brown, A. M., and Bruening-Wright, A. (2010). The action potential and comparative pharmacology of stem cellderived human cardiomyocytes. J. Pharmacol. Toxicol. Methods 61, 277-286.
38. Qu, Y., Gao, B. X., Fang, M., and Vargas, H. M. (2013). Human embryonic stem cell derived cardiac myocytes detect hERG-mediated repolarization effects, but not Nav1.5 induced depolarization delay. J. Pharmacol. Toxicol. Methods. 2013 Mar 19. pii: S1056-8719(13)00224-4. doi:10.1016/j.vascn.2013.03.001
39. Rajamani, S., Anderson, C. L., Valdivia, C. R., Eckhardt, L. L., Foell, J. D., Robertson, G. A., Kamp, T. J., Makielski, J. C., Anson, B. D., and January, C. T. (2006). Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and I(Kr). Am. J. Physiol. Heart Circ. Physiol. 290, H1278-H1288.
40. Rao, C., Prodromakis, T., Kolker, L., Chaudhry, U. A., Trantidou, T., Sridhar, A., Weekes, C., Camelliti, P., Harding, S. E., Darzi, A., et al. (2013). The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells. Biomaterials 34, 2399-2411.
41. Redfern, W. S., Carlsson, L., Davis, A. S., Lynch, W. G., MacKenzie, I., Palethorpe, S., Siegl, P. K., Strang, I., Sullivan, A. T., Wallis, R., et al. (2003). Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: Evidence for a provisional safety margin in drug development. Cardiovasc. Res. 58, 32-45.
42. Redfern, W. S., Wakefield, I. D., Prior, H., Pollard, C. E., Hammond, T. G., and Valentin, J. P. (2002). Safety pharmacology-a progressive approach. Fundam. Clin. Pharmacol. 16, 161-173.
43. Saint, D. A., and Tang, Y. (1998). Propofol block of cardiac sodium currents in rat isolated myocardial cells is increased at depolarized resting potentials. Clin. Exp. Pharmacol. Physiol. 25, 336-340.
44. Tashibu, H., Miyazaki, H., Aoki, K., Akie, Y., and Yamamoto, K. (2005). QT PRODACT: In vivo QT assay in anesthetized dog for detecting the potential for QT interval prolongation by human pharmaceuticals. J. Pharmacol. Sci. 99, 473-486.
45. Terrar, D. A., Wilson, C. M., Graham, S. G., Bryant, S. M., and Heath, B. M. (2007). Comparison of guinea-pig ventricular myocytes and dog Purkinje fibres for in vitro assessment of drug-induced delayed repolarization. J. Pharmacol. Toxicol. Methods 56, 171-185.
46. Toyoshima, S., Kanno, A., Kitayama, T., Sekiya, K., Nakai, K., Haruna, M., Mino, T., Miyazaki, H., Yano, K., and Yamamoto, K. (2005). QT PRODACT: In vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals. J. Pharmacol. Sci. 99, 459-471.
47. Valentin, J. P., Bialecki, R., Ewart, L., Hammond, T., Leishmann, D., Lindgren, S., Martinez, V., Pollard, C., Redfern, W., and Wallis, R. (2009). A framework to assess the translation of safety pharmacology data to humans. J. Pharmacol. Toxicol. Methods 60, 152-158.
48. Valentin, J. P., and Hammond, T. (2008). Safety and secondary pharmacology: successes, threats, challenges and opportunities. J. Pharmacol. Toxicol. Methods 58, 77-87.
49. Wakefield, I. D., Pollard, C., Redfern, W. S., Hammond, T. G., and Valentin, J. P. (2002). The application of in vitro methods to safety pharmacology. Fundam. Clin. Pharmacol. 16, 209-218.
50. Yang, T., Atack, T. C., Stroud, D. M., Zhang, W., Hall, L., and Roden, D. M. (2012). Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic. Circ. Res. 111, 322-332.