Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome.
The slow-channel congenital myasthenic syndrome (SCCMS) is caused by gain of function mutations in subunits of the end-plate acetylcholine receptor (AChR). The mutations prolong the opening episodes of the AChR channel, leading to a depolarization block and an end-plate myopathy. Because levels of quinidine sulfate attainable in clinical practice shorten the opening episodes of genetically engineered mutant SCCMS receptors in vitro, we tested the notion that the drug can be of benefit in SCCMS. We treated 6 SCCMS patients with quinidine sulfate in an open-label trial, using objective clinical measures of muscle strength and repetitive stimulation studies as end points. One patient became allergic to quinidine after 7 days. The remaining patients tolerated the drug well and after 30 days of continuous therapy showed statistically significant improvement in muscle strength and in decrement of the compound muscle action potential elicited by rapid rates of stimulation.
Harper
C M
CM
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Engel
A G
AG
D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D002648:Child; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000151:congenital / Q000188:drug therapy* / Q000235:genetics; D011446:Prospective Studies; D011802:Quinidine / Q000627:therapeutic use*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013577:Syndrome
D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D011802:Quinidine