Open-label trial of ranolazine for the treatment of paramyotonia congenita

Abstract

Introduction: Paramyotonia congenita (PMC) is a nondystrophic myotonic disorder that is believed to be caused by a defect in Na_v 1.4 sodium channel inactivation. Ranolazine, which acts by enhancing slow inactivation of sodium channels, has been proposed as a therapeutic option, but in vivo studies are lacking.

Methods: We conducted an open-label, single-center trial of ranolazine to evaluate efficacy and tolerability in patients with PMC. Subjective symptoms of stiffness, weakness, and pain as well as clinical and electrical myotonia were evaluated. Baseline measures were compared with those after 4 weeks of treatment with ranolazine.

Results: Ranolazine was tolerated well without any serious adverse events. Both subjective symptoms and clinical myotonia were significantly improved. Duration of myotonia was reduced according to electromyography, but this change was not statistically significant in all tested muscles.

Discussion: Our findings support the use of ranolazine as a treatment for myotonia in PMC and suggest that a randomized, placebo-controlled trial is warranted. Muscle Nerve 59:240-243, 2019.

Trial registration: ClinicalTrials.gov NCT02251457.

Keywords: channelopathy; electromyography; myotonia; paramyotonia; ranolazine; stiffness.

Figure 1.

(a) Patient-reported symptoms of stiffness, pain, and weakness were reduced at week 4 compared to baseline; (b) Clinical measures of Timed-Up-And-Go, eyelid opening time, and hand grip were significantly reduced at week 4 compared to baseline; (c) electromyography (EMG) myotonia duration in the tibialis anterior (TA), but not in the abductor digit minimi (ADM), was significantly reduced at week 4 compared to baseline.