Enhancing drug delivery to stimulate heart repair
Given the global burden of ischemic heart disease, the development of strategies to regenerate the human heart is among the most important challenges facing human health. While the heart is notoriously resistant to regeneration, the fundamental biology of the myocardium provides multiple therapeutic opportunities to improve heart repair.
Our work has focussed on defining molecular approaches that enhance the limited regenerative capacity of the heart by systematically searching for microRNAs able to promote myocyte regeneration or protection in the ischemic heart. Based on our work a biotechnology company focussed on the development of microRNA-based therapeutics was founded, called miRagen Therapeutics.
While very potent chemistries exist to therapeutically inhibit or increase microRNAs, systemic delivery of these drugs reduces cardiac exposure and can introduce unwanted side effects in tissues besides the heart. To date several delivery tools are available to supply drugs more locally. Here we aim to define the most efficacious cardiac delivery method to enhance pharmacological activity of microRNA drugs, while reducing the risk for unwanted toxicities. Our in vivo efficacy studies in animal models of myocardial infarction will allow us to identify the optimal cardiac delivery approach for our drugs to improve cardiac regeneration during ischemic injury.