Nervous System May Be Culprit In Deadly Muscle Disease

Pompe disease is a rare inherited disorder that affects muscle function in infants. It is caused by a mutation in the GAA gene that prevents the enzyme acid alpha-glucosidase from breaking down glycogen. As a result, an accumulation of glycogen builds up in the body’s cells and impairs the muscles ability to function normally, particularly those of the heart and respiratory muscles. Children diagnosed with this disorder very rarely live beyond the age of two years old.



Left: Normal muscle cells
Right: affected muscle cells
In Pompe disease, glycogen accumulation causes the lysosomes to expand, damaging muscle cells. Glycogen leaks out of the cells, impairing muscle function.


Until a recent study, it was believed that Pompe disease was principally a muscle disease. In the Proceedings of the National Academy of Sciences investigation, researchers examined breathing in mice with Pompe disease and mice that were genetically engineered to produce GAA in muscle only and not in the central nervous system. It was found in both models that the phrenic nerve impulses (from the brain to the diaphragm via the spinal cord) to stimulate breathing were noticeably weaker than in normal mice. Furthermore, a detailed examination of a Pompe disease patient's nervous system showed a similar glycogen accumulation in the spinal cord as well as deficient neural output to the diaphragm.

These findings in the mouse models suggest that the disease may actually be caused by weakened signals from the brain to the diaphragm along the nervous system. Therefore treatments targeting the muscle alone may be inefficient. The study indicates that when treating children with Popme’s disease, not only do must the therapy be targeted to the muscle and heart, but also delivered to the nerve.




References:
University of Florida (2009, May 26). Nervous System May Be Culprit In Deadly Muscle Disease. ScienceDaily. Retrieved May 31, 2009, from http://www.sciencedaily.com /releases/2009/05/090525173444.htm

For more information on Pompe disease:
http://www.pompe.com/healthcare/overview/pc_eng_hc_overview_main.asp
http://ghr.nlm.nih.gov/condition=pompedisease