QUINIDINE SULFATE THERAPY FOR THE SLOW-CHANNEL CONGENITAL MYASTHENIC SYNDROME

The slow-channel congenital myasthenic syndrome (SCCMS) is caused by g ain of function mutations in subunits of the end-plate acetylcholine r eceptor (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 sh orten the opening episodes of genetically engineered mutant SCCMS rece ptors in vitro, we tested the notion that the drug can be of benefit i n 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 alle rgic to quinidine after 7 days. The remaining patients tolerated the d rug well and after 30 days of continuous therapy showed statistically significant improvement in muscle strength and in decrement of the com pound muscle action potential elicited by rapid rates of stimulation.