A Healthier Wisconsin

Novel Tail Domain MYH6 Gene Variants in Hypoplastic Left Heart Syndrome (HLHS) and Cardiomyopathy

Preventing and decreasing the impact of chronic health disease

Full Project Name:Novel Tail Domain MYH6 Gene Variants in Hypoplastic Left Heart Syndrome (HLHS) and CardiomyopathyPrincipal Investigator:Aoy Tomita Mitchell, PhD, SurgeryCo-Investigator:Joy Lincoln, PhD, Pediatrics; Brandon Tefft, PhD, Biomedical Engineering; Michael Mitchell, MD, Surgery; Robert Fitts, PhD, Marquette University; Amy Pan, PhD, PediatricsAward Amount:$200,000
Award Date
Project Duration:24 months

Project Description Narrative:

This research involves treating cells grown from tissue from people with a variant in a gene called MYH6 to develop medical care to prevent/decrease congenital heart disease's impact on patients' lives. People who have variations in the MYH6 gene have a loss of function in the muscle cells of their heart. These gene variations are often found in people with severe congenital heart defects who require significant heart surgery and/or heart transplant to live. In families with the MYH6 gene variant, one person may have hyperplastic left heart syndrome while others have normal hearts. The heart of a person with hyperplastic left heart syndrome has just one ventricle instead of two, leading to a lifetime of cardiac care.

The proposed model holds the promise of providing the information needed to develop treatments to prevent or lessen the impact of hyperplastic left heart syndrome, other subtypes of chronic heart disease, and other related cardiac diseases such as cardiomyopathies. The most successful application of this research would be during pregnancy. It would provide the opportunity to correct genetic misinformation during the development of a fetus, thus allowing for normal development of the heart. The outcomes of this project could also improve clinical outcomes for patients born with hyperplastic left heart syndrome or chronic heart disease and other related cardiac diseases such as cardiomyopathies.

Project Updates:

  • Showed that genetic mis-messaging from the tail domain variant used in this study impacts the contractility of the cells and the formation of the building blocks of the heart cells itself
  • Designed very specific siRNAs targeting MYH6 tail domain variants and have started testing them in the hypoplastic left heart syndrome (HLHS) cell model
  • Leveraged $380,000 in additional funding through numerous grants

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