Gene Therapy Suggests Older Medication May Reduce Arrhythmias In Congenital Disorder Interview with:
Silvia G Priori ,MD, PhD and
Andrea Mazzanti, MD

Medical Research: What is the background for this study? What are the main findings?

Response: The study investigates a novel therapeutic approach for Long QT Syndrome type 3: a malignant varian of long QT Syndrome a disease in which the risk of arrhythmias is proportional to the prolongation of QT interval. LAQT3 is caused by gain of function mutations in the gene SCN5A that encode for the alpha subunit of the cardiac sodium channel. These mutations increase the late sodium current (INa late) that prolongs the QT interval and predisposes the heart to develop life-threatening ventricular arrhythmias. In 1996 we demonstrated in an animal model of Long QT Syndrome type 3 that administration of mexiletine was able to shorten QT interval and the same results were obtained in LQT3 patients treated with mexiletine : these data provided rational for the adoption in clinical practice guidelines to recommend the use of mexiletine to shorten QT interval in LQT3 patients with the expectation that shortening QT interval would reduce the risk of arrhythmic death. In this setting, our study is the first to provide data in support of the view that mexiletine shortens QT interval and reduces the probability to experience arrhythmic events.

Medical Research: What should clinicians and patients take away from your report?

Response: This study is an example of “precision medicine” as it shows that based on the identification of a specific genetic defect ( i.e. a mutation in the gene encoding the alpha subunit of the cardiac sodium channel) it is possible to treat patients with a medication that specifically counteracts the abnormality induced by the genetic defect. The study provides for the first time a support to the concept that mexiletine may improve survival in LQT3 patients.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: As a result of this study there is a rational to continue monitoring LQT3 patients treated with mexiletine to observe the effect on mortality

Medical Research: Is there anything else you would like to add?

Response: I would like to add that unfortunately mexiletine is considered an “old” antiarrhythmic drug and therefore is no longer available in several countries. Our study suggests that mexiletine seems able to reduce arrhythmic events in LQT3 and therefore it would be important to consider to make it available for treatment of LQT3 patients in every country. Our data also support the concept that, at a time in which “affordable innovation” is very much needed in medicine, policies aimed at rescuing old and cheap drugs that can be “repositioned” in novel indications should be encouraged and supported.


Mazzanti A, Maragna R, Faragli A, et al. Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3. J Am Coll Cardiol.2016;67(9):1053-1058. doi:10.1016/j.jacc.2015.12.033.

Silvia G Priori ,MD, PhD and, & Andrea Mazzanti, MD (2016). Gene Therapy Suggests Older Medication May Reduce Arrhythmias In Congenital Disorder