"Disease-in-a-dish" approach to treating pediatric hypertrophic cardiomyopathy

Pathogenic variants in MYH7 and MYBPC3 account for the majority of hypertrophic cardiomyopathy (HCM). However, targeted drugs like myosin ATPase inhibitors have not been evaluated in children.

Caroline Kinnear from Dr. Seema Mital’s group at the Hospital for Sick Children, Toronto, will describe how the team generated patient and variant-corrected iPSC-cardiomyocytes (CMs) from pediatric HCM patients harboring single variants in MYH7 (V606M; R453C) and MYBPC3 (G148R) or digenic variants (MYBPC3 P955fs, TNNI3 A157V). Compared with isogenic and healthy controls, variant-positive CMs showed hypertrophy, sarcomere disorganization, higher contractility, calcium transients, and ATPase activity.

Kinnear will also highlight how targeted myosin ATPase inhibitors showed complete rescue of the phenotype in variant-positive CMs and in cardiac biowires to mirror isogenic controls. The response was superior to verapamil or metoprolol. The findings indicate myosin inhibitors can be effective in genotypically diverse HCM highlighting the need for myosin inhibitor drug trials in pediatric HCM.

Key learning objectives

  • Learn how a “disease-in-a-dish” approach can potentially improve the treatment of disease
  • Gain insights into genotype-phenotype association using patient-derived iPSCs
  • Explore how analytical tools, such as the xCELLigence RTCA CardioECR instrument, are used to elucidate the mechanisms of diseases and evaluate the effects of pharmacological and genetic interventions
  • Understand the translational importance of targeted myosin inhibitor therapies for future clinical trials


Who should attend?

  • Researchers and scientists in industry and academia, basic and translational cardio disease researchers, and cardio drug discovery enthusiasts.

Certificate of attendance
All webinar participants can request a certificate of attendance, including a learning outcomes summary, for continuing education purposes.

Speakers

Caroline Kinnear, MS
Caroline Kinnear, MS
Laboratory Manager, The Hospital for Sick Children

Caroline Kinnear has completed a Bachelor of Science degree in Montpellier University in France and a Master of Science at the University of Toronto in Ontario, Canada. She has been working at the Hospital for Sick Children in Toronto in the cardiac research field for over 20 years. As a member of Dr. Seema Mital’s team, she has focused on heart disease modeling and approach to therapy and contributed to many publications.

Xiaoyu Zhang
Xiaoyu Zhang
R&D project manager, Agilent

Xiaoyu Zhang earned her Ph.D. in Cell, Molecular, and Developmental Biology from the University of California, Riverside, and completed her postdoctoral training at the Sanford Burnham Prebys Medical Discovery Institute. At Agilent, she has established herself as an expert in cardiomyocyte-related assays and the xCELLigence RTCA cardio-related platforms, where she has led cardiac safety screening programs and provided technical support for RTCA Cardio systems. Currently, she serves as an R&D project manager, focusing on the development of real-time cell analysis applications using the xCELLigence platform. Her primary areas of interest are cardiovascular research, cancer immunotherapy, and infectious diseases.

Moderator

Matilde Marques
Matilde Marques
Life Sciences Assistant Editor, SelectScience

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