Important preclinical steps for all Nav1.4 activators will be to determine whether they are able 1) to restore a ‘normal’ Nav1.4 current from mutant channels in vitro; 2) to improve muscle force without inducing myotonia or paralysis in preclinical animal models; and 3) are safe enough to be used in humans. The gene discussed is SCN4A; the disease is Myotonia.