A new study led by York University's Muscle Health Research Centre finds that early heart damage in Duchenne muscular dystrophy may not affect all parts of the heart in the same way.
Published in Molecular Metabolism, the research shows that fibrosis - scar tissue that replaces damaged muscle - develops mostly in the right ventricle and left atrium during early stages of the disease in a preclinical model. The other two chambers of the heart showed no signs of damage at that time.
Christopher Perry
"Fibrosis is a hallmark of Duchenne muscular dystrophy, but what we found was that it doesn't affect all regions of the heart equally," says MHRC Director Christopher Perry, a professor in the Faculty of Health. "This suggests that the genetic mutation that causes the disease may interact differently with each chamber of the heart."
Duchenne muscular dystrophy is a genetic condition that causes muscles to weaken over time. It is linked to changes in the dystrophin gene and can affect the heart, though the role of fibrosis is still being studied.
The research team, led by recent PhD graduate Shivam Ghandi, also studied a small compound called ALY688. This compound activates receptors for adiponectin, a hormone that helps control inflammation and metabolism. In an early-stage disease model, short-term treatment with ALY688 completely prevented fibrosis in the two affected heart chambers.
The study also found that certain immune cells were more active in the damaged heart tissue. Treatment with ALY688 reduced these immune cells and improved signs of heart metabolism.
"The study indicates that early intervention could help prevent long-term cardiac issues associated with Duchenne muscular dystrophy," says Perry, noting that targeting adiponectin receptors may present a new therapeutic strategy to protect heart function in those living with the disease."
The findings raise new questions about why some heart chambers are more vulnerable to fibrosis than others, and how inflammation and metabolic stress may contribute to heart damage.
The study was a collaborative effort involving researchers from York University - including Perry, Associate Professor Ali Abdul-Sater, Professor Peter Backx and several grad students - as well as researchers from with the University of Waterloo, the University of Guelph and Allysta Pharmaceuticals Inc.
Read the full study.
This story was originally featured in YFile, York University's community newsletter
