Teresa M. Lee, MD, MS
Masayuki Yazawa, PhD
Human Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy
Columbia University, New York, NY
2017 Amount Awarded – $50,000
Cardiomyopathies are a diverse group of disorders with outcomes largely based on underlying cause and age of onset. For example, 14.2% of infants with hypertrophic cardiomyopathy do not survive beyond the first year after diagnosis as compared to 0.8% of older children. Furthermore, current understanding of the underlying genetic etiology of pediatric cardiomyopathy is largely based on adult studies extrapolated to children. Earlier age of onset suggests the involvement of different biological mechanisms. Despite the availability of routine clinical testing panels, the genetic cause remains unknown in the majority of children. Thus, the underlying mechanism of disease development in pediatric cardiomyopathy is largely unknown. As such, therapeutic regimens primarily focus on symptomatic management without affecting the underlying disease progression. This study will develop a human disease model of infantile hypertrophic cardiomyopathy using induced pluripotent stem cells and gene editing techniques. This will allow studying the genes and proteins involved in the development of hypertrophy and leading to impaired heart function. Induced pluripotent stem cells provide a robust method for functional studies to elucidate the damaging effects of novel genetic changes, furthering knowledge about the genetic mechanisms of pediatric cardiomyopathy. Moreover, generated heart cells serve as a human model for cardiomyopathy, which can be used as a platform to test new drugs that can then be translated into treatments specifically targeted to children.