Our understanding of the molecular pathogenesis of the neuromuscular ion 
channelopathies has increased rapidly over the past two decades due to the 
identification of many of the genes whose mutation causes these diseases. These 
molecular discoveries have facilitated identification and classification of the 
hereditary periodic paralyses and the myotonias, and are likely to shed light on 
acquired ion channelopathies as well. Despite our better understanding of the 
pathogenesis of these disorders, current treatments are largely empirical and 
the evidence in favor of specific therapy largely anecdotal. For periodic 
paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a 
controlled trial to prevent attacks for many patients with both hypokalemic and 
hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with 
acetazolamide versus placebo, is currently in progress. For myotonia, there is 
only anecdotal evidence for treatment, but a controlled trial of mexiletine 
versus placebo is currently being funded by a Food and Drug 
Administration-orphan products grant and is scheduled to begin in late 2008. In 
the future, mechanism-based approaches are likely to be developed. For example, 
exciting advances have already been made in one disorder, myotonic dystrophy-1 
(DM-1). In a mouse model of DM-1, a morpholino antisense oligonucleuotide 
targeting the 3' splice site of CLCN1 exon 7a repaired the RNA splicing defect 
by promoting the production of full-length chloride channel transcripts. 
Abnormal chloride conductance was restored, and myotonia was abolished. Similar 
strategies hold potential for DM-2. The era of molecularly-based treatments is 
about to begin.