2012 AWARDED GRANT
Daniela Cihakova, MD, PhD
Drivers of Pediatric Dilated Cardiomyopathy
Johns Hopkins University, Baltimore, MD
Daniela Cihakova, MD, PhD – $50,000
Dilated Cardiomyopathy (DCM) is a major cause of heart failure in children and frequently requires cardiac transplantation. Currently, no drug is available to delay or stop progression to DCM, or improve the long-term survival of children with DCM. Studying mice models of DCM can help to better understand the mechanism of DCM development. In past mouse studies, it was discovered that an immune cell product, called cytokine IL17A, is essential to the development of DCM and that mice that were deficient in that cytokine did not develop DCM. It was also found that heart cells (cardiomyocytes and cardiofibroblasts) can receive signals from IL17A with the possibility that IL17A promotes DCM by its direct action on cells in the heart. Furthermore, IL17A induces production of another cytokine Granulocyte-macrophage colony-stimulating factor (GM-CSF) in the mouse's heart. This study proposes that IL17A induces DCM development through GM-CSF. This concept will be tested on a mouse model as well as on cardiac cells isolated from mouse hearts growing in test tube. Since DCM is often preceded by myocarditis, the study will explore whether blocking a particular cytokine such as IL17A or GM-CSF after heart inflammation could lead to arrest or improvement of the pathological changes that lead to DCM. If successful, the same strategy will be proposed for treatment of humans with DCM and could lead to the first biological treatment for DCM.