Morayma Reyes, assistant professor of pathology at the University of Washington in Seattle, was awarded an MDA research grant totaling $300,000 over a period of three years to study a strategy for reducing heart muscle damage in Duchenne muscular dystrophy (DMD).
People with DMD develop cardiovascular problems in their early teen years, and cardiac complications are the major cause of death in the disease. A significant contributor to the damage done to heart muscle is fibrosis, or development of fibrous tissue within the muscle. Fibrosis is a response to inflammation, part of the body’s immune response. Reyes will be studying the effect of blocking a molecular pathway that contributes to that inflammation.
She has characterized cells surrounding blood vessels within the fibrotic tissue of heart muscle in the mdx mouse, a mouse model of DMD. “We hypothesize that these cells respond to inflammatory cues and deposit collagen, and thus form fibrotic tissue in the perivascular tissue of mdx hearts,” she says. “We will study the role of these cells in mdx cardiac fibrosis.”
In particular, she will study a potentially important signaling pathway, called the PDGF receptor alpha pathway. “We hypothesize that signaling through PDGF receptor alpha results in activation of a fibrotic program in these cells. We will test this by administration of PDGF-A, which should result in increased fibrosis.”
She will then block the pathway to reduce fibrosis, testing the potential benefits of a drug called Crenolanib. “These studies will lay the foundation for preclinical studies using Crenolanib to treat fibrosis in DMD patients,” Reyes says.
Funding for this MDA grant began August 1, 2013.