Muscular Dystrophy is a devastating disease that is represented by severe muscular paralysis that is a direct result of the profound loss of muscle cells. Faciosapulohumeral Muscular Dystrophy (FSHD) is the third most common form of the inheritable form of Muscular Dystrophy. In order to implement effective treatment for this extremely debilitating disorder, it is essential to uncover the underlying mechanism of the disease process.
It has been previously established that a mutation in human chromosome number 4 is the underlying cause of FSHD. It has also been shown that in FSHD patients there is the expression of the DUX4 protein that is not normally found in human muscle cells. However, the underlying relationship between this protein and the disease has been poorly understood.
The DUX4 gene product – a gene can be defined as the genetic information that contains the blueprint for a unique protein – is responsible for the regulation of many genes whose protein products are normally found in the male germ line but that are abnormally expressed in the muscle cells of FSHD patients. In fact, the DUX4 protein functions as a transcription factor – a protein that regulates the expression of other genes. Dr. Stephen Tapscott and his colleagues at the Fred Hutchinson Cancer Research Center in Seattle, WA have established that the mutation in chromosome number 4 is directly responsible for the expression of DUX4 in the muscle cells of FSHD patients and that its presence in these cells can initiate the loss of muscle cells by a number of possible mechanisms. It may accelerate cell death through a process known as apoptosis or it may trigger an autoimmune response in which the patient's own immune system begins to target muscle tissue.
These findings have considerable therapeutic implications. Some possibilities for treatment have been proposed including blocking the expression of DUX4 or interfering with its downstream effects.