duchenne | Neuro Daily

Press Release:

Scientists at Sanford Burnham Prebys Medical Discovery Institute, Fondazione Santa Lucia IRCCS, and Università Cattolica del Sacro Cuore in Rome have shown that pharmacological (drug) correction of the content of extracellular vesicles released within dystrophic muscles can restore their ability to regenerate muscle and prevent muscle scarring (fibrosis). The study, published in EMBO Reports, reveals a promising new therapeutic approach for Duchenne muscular dystrophy (DMD), an incurable muscle-wasting condition, and has far-reaching implications for the field of regenerative medicine.

“Our study shows that extracellular vesicles are bioactive mediators that can transfer the benefits of medicine–in this case, HDAC inhibitors (HDACi)–to treat DMD,” says Pier Lorenzo Puri, M.D., professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys and co-corresponding author of the study. “We discovered the promise of this treatment almost 20 years ago and did all of the preclinical work, which led to a current clinical trial for boys with DMD. However, the therapeutic potential of HDACi has been so far limited by its systemic adverse effects.”

In the current clinical trial, boys with DMD are treated with HDACi at suboptimal doses due to the risk of adverse side effects. The scientists are hopeful that extracellular vesicles might provide a cell-free, non-immunogenic, transplantable tool for local delivery of bioactive particles that transfer HDACi to dystrophic muscles, thereby overcoming the undesirable secondary effects caused by chronic use at high doses.

Press Release:

DALLAS – Dec. 21, 2020 – A UT Southwestern research team has catalogued gene activity in the skeletal muscle of mice, comparing healthy animals to those carrying a genetic mutation that causes Duchenne muscular dystrophy (DMD) in humans. The findings, published online recently in PNAS, could lead to new treatments for this devastating degenerative disease and insights into factors that affect muscle development.

Understanding the activity of genes can shed light on pathologies that affect different tissues in the body. However, says Rhonda Bassel-Duby, Ph.D., a professor of molecular biology at UTSW, studying skeletal muscle has been a challenge because of a key difference from other tissue types; rather than containing a single nucleus that controls the activity of the genes, a skeletal muscle fiber can contain hundreds of nuclei. And it was unknown which genes were activated in all these nuclei, making it unclear how gene expression differs between healthy skeletal muscle tissue and tissue affected by DMD.