Acetylcholine receptor genes in the slow-channel syndrome
(Collaboration with Dr. Christopher Gomez, University of Chicago, Chicago, IL)
The slow channel syndrome (SCS) is an ion channelopathy caused by mutations in the muscle acetylcholine receptor (AChR) that give rise to degeneration of the neuromuscular junction (NMJ). The long-range goal of this project is to define the pathways, and explore therapies for the progressive synaptic degeneration seen in SCS, as a model for other synaptic disorders.
Having identified a list of mutations and characterized potential disease pathways in vivo, we have developed new approaches to define environmental factors that enhance disease process at three levels:
- Increase the expression of SCS mutation in the endplate.
- Delay the MEPC decay time.
- Increase cationic overload of the endplate.
These studies will serve both to advance treatment of SCS and to assess the relative contribution of different environmental factors such as alcohol, nicotine, and statins to the enhancement of neuromuscular weakness and synaptic degeneration in vivo.