The biological processes that drive disease progression in Duchenne muscular dystrophy (DMD) start before birth, according to a study recently published in Nature Communications.
The conventional understanding is that DMD only begins to damage muscles after birth, which leads to cumulative damage and noticeable symptoms between 3 and 5 years of age. But by studying the formation of muscle tissue in a fetal mouse model of DMD, the researchers found evidence indicating that the disease processes driving DMD begin much earlier.
“Our comprehensive study of myogenesis in the mdx embryo reveals that DMD is an intrinsic MuSC [muscle stem cell] disease that manifests during secondary myogenesis before any accumulation of necrotic myofibers, fibrosis, or inflammatory changes,” the study’s authors noted.
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When an embryo is developing into a fetus, skeletal muscle forms in two stages. The first, called primary myogenesis, forms larger muscle fibers. Later on, new, smaller fibers form alongside the larger ones, a process called secondary myogenesis.
The study’s authors found that primary myogenesis was not affected by dystrophin deficiency. However, they found a link between dystrophin deficiency and secondary myogenesis.
The lack of dystrophin during this stage triggered a chain reaction of events that impacted muscle formation, including a reduction in myogenic progenitors, a type of stem cell important for muscle growth and repair. As a result, mouse models of DMD had less dense muscle than normal mice.
The authors noted that their findings raise the question on whether earlier screening for DMD would be beneficial.
“Since MuSC dysfunction and aberrant muscle architecture arise in utero, it may be essential to implement newborn screening for DMD followed by MuSC-targeted therapies administered shortly after birth to leverage rapid neonatal muscle growth and enable timely intervention,” they wrote.
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