Oculopharyngeal muscular dystrophy (OPMD) is an inherited type of muscular dystrophy that primarily affects muscles of the face and throat. In the video below, Anita Corbett explains how this affects patients as they get older.
The mutations that cause the disease make a protein called PABPN1 longer and stickier than normal, and the mutated protein appears to form clumps in muscle cells.
The puzzle lies in that PABPN1 (poly A binding protein nuclear 1)Â can be found everywhere in the body, but it’s not clear why the mutated protein specifically affects muscle cells — or why the muscles in the face and throat are especially vulnerable.
In December 2009, Corbett, Pavlath and postdoctoral fellow Luciano Apponi published a paper where they suggest that the clumps of mutated protein, which some researchers have proposed to be toxic, might not be the whole story. A lack of functioning PABPN1 might be just as strong a factor in the disease, they’ve discovered.
The results will appear in a future issue of the journalÂ Human Molecular Genetics.
The Emory team showed that when depleted of PABPN1, mouse muscle cells failed to mature and proliferate normally. PABPN1â€™s normal function appears to be making sure messenger RNAs from a variety of genes have a protective â€œpoly Aâ€ tail that allows them to leave the nucleus. When the levels of PABPN1 in cells were â€œknocked downâ€ artificially, messenger RNAs accumulate in the nucleus.
Corbett and Pavlath recently were awarded a Challenge grant from the National Institute of Neurological Disorders and Stroke to investigate the mechanism of OPMD.
They say the grant will allow them to create genetically engineered mice mirroring the situation in OPMD patients.
This could allow them to further probe the “toxic clumps or missing protein” question and understand which treatment strategies might be most successful.
A recent article in the Muscular Dystrophy Association’s Quest magazine focuses on OPMD. Corbett’s and Pavlath’s research has been supported by the Muscular Dystrophy Association.