Correlation Engine 2.0
Clear Search sequence regions

  • 3 splice site (1)
  • CLCN1 (1)
  • DM 2 (1)
  • DM- 1 (2)
  • drug orphan (1)
  • exon (1)
  • humans (1)
  • ion (2)
  • ion channels (2)
  • morpholino (1)
  • myotonias (3)
  • past (1)
  • pathogenesis (2)
  • patients (1)
  • rna (1)
  • transcripts (1)
  • Sizes of these terms reflect their relevance to your search.

    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.


    James C Cleland, Robert C Griggs. Treatment of neuromuscular channelopathies: current concepts and future prospects. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2008 Oct;5(4):607-12

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 19019313

    View Full Text