Grant: Project Grant

Cardiac hypertrophy is a condition that is defined as a thickening (hypertrophy) of the heart muscle (cardiac), which can lead to heart failure. Recent work has discovered genes that play a large role in hypertrophy, including miR-1 that is present in unusually low amounts in hypertrophied hearts. The major limitation of miR-1 therapy is the lack of an effective delivery strategy. Recently, ultrasound (US) technology has been proposed as an exciting solution to this challenge. Microbubbles, tiny gas bubbles that freely flow through the blood stream, vibrate when exposed to US and are currently used to help cardiologists interpret US images. They can be modified to carry genes like miR-1 and, by tightly focusing US energy from outside the body to the heart, can be made to selectively "poke holes" in target cells and deliver their payloads. Our overall goal is to design a system that uses US to specifically target cardiac hypertrophy. We are exploring this type of treatment because US is already one of the main tools that doctors use to diagnose cardiac hypertrophy in the first place. Our first goal is to establish the appropriate US parameters that deliver miR-1 into cells without causing any harm or long-term side effects using a cardiomyocyte cell culture model. Our second goal is to determine the treatment plan to successfully deliver miR-1 to hypertrophic hearts in rodent models of disease - e.g. to determine how long the treatment lasts, and whether patients would need additional treatments over time. While US is currently used worldwide diagnostically, our project aims to leverage this technology by developing a dual imaging and therapeutic platform. In this manner, doctors will be able to monitor treatment real-time to ensure that the genetic material is being delivered right into the heart. Importantly, the insights gained from our work will be able to inform further development of this technique towards the treatment of other cardiovascular diseases.