Dystrophin is part of a protein complex linking the cytoskeleton of muscle fibers to the surrounding connective tissue (basal lamina). It’s a long protein with numerous redundant coils (purple balls), and acts like a shock absorber during contraction. Without functional dystrophin to support muscle strength and stability, muscle fibers are easily damaged.
The genetics of Duchenne
Duchenne muscular dystrophy results from mutations in the DMD gene that encodes the dystrophin protein. There are many types of mutations that can cause the disease; each disrupts the reading frame such that translation terminates prematurely, producing no functional dystrophin protein. DMD mutations are particularly common in “hotspot” areas of the gene (exons 45–55 and 2–10).
Wildtype DMD gene
Because the genetic underpinnings of Duchenne are known, researchers can devise gene-editing fixes to the problem. Several potential treatments are now being tested in preclinical and clinical studies. In some cases, they aim to correct the mutations in the DMD gene; other times, the goal is simply to restore a shorter but still partially functional dystrophin protein.
Example: A mutation in exon 44 disrupts the reading frame and causes translation to stop prematurely, leading to a dysfunctional protein.
Strategies for fixing the problem
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