Funding outcome

Barth Syndrome is a rare genetic disease with very poor rates of infant survival, often due to heart disease. Even if an infant with Barth Syndrome survives into childhood, heart disease will remain a constant concern for reduced health in these children, and will significantly impact the ability for these children to survive into adulthood. It has recently been discovered that the hearts of Barth Syndrome patients do not produce energy as efficiently when compared to the hearts of healthy patients. Because of this malfunction in the heart's ability to produce energy, the heart in a Barth Syndrome patient cannot pump blood to the rest of the body as well as it does in a healthy person, which causes a heart disease known as heart failure. The goal of our research is to determine whether improving the heart's ability to produce energy in a child with Barth Syndrome may be an exciting method to reduce the risk for heart disease and heart failure in these children. To be specific, we hypothesize that an energy source made by the liver, the ketone body, may be a better energy source for the heart to metabolize for energy in a child with Barth Syndrome. Therefore, increasing ketone body metabolism in the heart may be a beneficial strategy to reduce the risk for heart failure in Barth Syndrome children. Recently, a unique genetically modified mouse has been produced for scientific research that has the same genetic mutation that Barth Syndrome patients have, and these mice also develop heart failure. We will breed these genetically modified mice in our lab, and provide them with either a special diet, or treat them with a drug (empagliflozin), both of which increase ketone body levels in the blood, which will increase ketone body metabolism in the hearts of these mice. We will test whether the diet or drug treatment improve heart function in these mice and prevent heart failure. If our hypothesis is correct, our research will suggest that boosting ketone body metabolism in the heart might be an effective way to prevent heart failure in Barth Syndrome children and improve their chances of surviving into adulthood, while also improving their quality of life.