Grant: Operating Grant

Hyperkalemic periodic paralysis (HyperKPP) is a disease that is primarily characterized by uncontrolled contractions of skeletal muscles with periods of complete paralysis that mainly affect limb muscles. The paralysis completely incapacitates patients because they are unable to move, often confined to bed for a period of time varying from a few hours to days. Past the age of 30, uncontrolled contractions and paralysis may cease, but patients suffer of muscle weakness such that walking becomes a difficult task; in some cases, patients become wheelchair bound. None of the present available treatments for HyperKPP are fully effective. Muscle contraction is initiated by the generation of an electrical signal, i.e., action potential, on the cell membrane. In turn, the action potential starts with the entry of sodium into muscle fibers via a pore made by a protein called the sodium channel. HyperKPP results from mutations of this sodium channel that is primarily expressed in skeletal muscle. The mutation results in uncontrolled sodium influx at rest giving rise to the uncontrolled contractions and then paralysis. One common gene defect for this disease is a missense mutation where valine replaces methionine at residue 1592 (NaV1.4/M1592V). The overall objective of this study is to document the mechanism of the disease and to develop new and more effective therapeutic approaches.