Precision Medicine

Location: The Hospital for Sick Children (SickKids)

One in 100 children is born with a heart defect. Others are born with defects in heart muscles. Some defects can be cured by surgery. Others are left with sequelae that can eventually lead to heart failure. Currently available medicines have very limited benefit in heart failure. We believe that understanding the genetic basis of heart failure will allow us to develop medicines that are targeted to the unique type of heart failure, thereby making them safer and more effective.

To do this with precision requires knowledge of a person’s genetic make-up, as well as lifestyle and environmental factors, in a way that can guide tailored medicine for every patient. And that is at the heart of Precision Medicine. The Ted Rogers Centre for Heart Research is leveraging the power of sequencing to unravel the unique genome of every child with heart disease and heart failure and to use this knowledge to implement a Precision Medicine approach to their care.

Our journey begins with two focused patient groups:

  • Tetralogy of Fallot: This condition is the commonest cause of babies being born “blue.” Surgery during infancy can fix the defect but the right ventricle in these children can fail over time requiring repeated surgeries and/or transplant. We are sequencing children with this condition in order to identify genes that make children susceptible to right heart failure. We are also trying to identify protein markers in blood that can predict patients at risk for failure. This knowledge will help us to develop new treatments and to intervene before right heart failure becomes irreversible, thereby sparing children (and adults) from future reoperations or transplants.
  • Cardiomyopathy: This disease of the heart muscle interferes with its ability to contract or relax. This causes the heart to eventually fail with heart transplant being the only option. It also poses a risk of dangerous heart rhythms that can cause sudden death. The disease often runs in families. Improvements in sequencing technology have helped identify more than 100 genes associated with cardiomyopathy. Yet, the cause of cardiomyopathy remains unknown in a majority of families.

Knowing the genetic cause of cardiomyopathy is critical in order to protect not just the patient but other family members from the devastating consequences of a missed diagnosis. Also, knowing the gene involved in the disease gives us an opportunity to develop treatments that can reverse the effects of the gene defect, and some day in the future, even fix the gene defect. The team of researchers at SickKids is studying the genomes of families with cardiomyopathies to achieve these goals.

The team is supported by stem cell experts who can generate heart cells from the skin or blood of patients with this disease. These cells can then be used to screen new and known drugs to find those that can rescue the heart abnormalities and can eventually be tested in clinical trials in patients. This project will build upon the work already performed at the SickKids Heart Centre Biobank.