This year brought two historical leaps forward in our understanding of a common form of muscular dystrophy—the biggest steps in two decades—paving the way for better diagnosis and treatment.
Facioscapulohumeral muscular dystrophy (FSHD), characterized by progressive weakening and loss of skeletal muscle, is the most prevalent type of the condition. FSHD is a genetic disease, caused by a flaw in the DNA instructions near the end of chromosome 4. In those with FSHD, the DNA sequence is cut short. But here’s the puzzle: not everyone with this so-called “contraction” gets FSHD.
The Hutchinson Center’s Dr. Stephen Tapscott, working with a multinational team, discovered that people with FSHD have both the DNA sequence contraction and a molecular signal that tells cells not to destroy a rogue protein, allowing it to cause chaos in the form of FSHD.
They also found that the disease is caused by a faulty “off” switch for a particular retrogene, normally expressed only in early development and then tamped down in all other cells of the body. When the retrogene isn’t suppressed, it bursts in the muscle cells and leads to cell death and muscular dystrophy. It is the first time in genetic research history that a retrogene has been found to "wake up" and cause disease.
The basic biology of a disease must be understood before treatment targets are clear. These landmark findings will make it easier to diagnose FSHD and better predict who will get the disease, even before symptoms appear, as well as provide critical focus for future development of FSHD therapies.