# Effectiveness of resveratrol in inducing adeno-associated virus as a potential definitive therapy for SCN5A mutation in Brugada syndrome: a narrative review

## TL;DR

This review explores resveratrol's potential to enhance gene therapy for Brugada syndrome by improving adeno-associated virus delivery to correct heart rhythm issues.

## Contribution

The paper introduces resveratrol as a novel modulator of AAV-based gene therapy for SCN5A mutations in Brugada syndrome.

## Key findings

- Resveratrol activates deacetylase proteins, influencing DNA repair and energy metabolism.
- Resveratrol enhances AAV-mediated gene delivery through p53 pathway activation.
- AAV-MOG1 gene therapy improves sodium channel function and cardiac rhythm in BrS.

## Abstract

Brugada syndrome (BrS) is a hereditary channelopathy that affects cardiac electrical signal transmission, with SCN5A gene mutation being the most common cause. Current BrS therapy primarily relies on Implantable Cardioverter Defibrillators, which are limited to arrhythmia prevention. Recent research has explored gene therapy as an alternative approach for managing BrS. Resveratrol, a non-ketone polyphenol compound, exhibits cardioprotective effects due to its antioxidant properties, which can influence gene expression through cellular signaling pathways, thereby modulating adeno-associated virus (AAV). This study aims to evaluate the effectiveness of resveratrol in enhancing the induction of AAV-based viral vectors as a potential definitive therapy for SCN5A mutations in BrS patients.

A comprehensive literature search was conducted across multiple databases, including PubMed, Google Scholar, ScienceDirect, and PLOS ONE. The final stage involved assessing the eligibility of 47 studies, followed by a full-text review, which included seven studies for further analysis.

The findings indicate that this therapeutic approach highlights resveratrol’s crucial role as an activator of deacetylase proteins, influencing DNA repair processes, cell cycle regulation, and energy metabolism. Resveratrol facilitates the modulation of Voltage-Gated Calcium Channels, enabling calcium ion (Ca2⁺) influx into cardiomyocytes, thereby maintaining normal cardiac rhythm. Resveratrol enhances AAV-mediated gene delivery and expression through p53 pathway activation.

Experimental studies have demonstrated that AAV-MOG1 gene therapy can restore sodium channel function, improve cardiac electrophysiological abnormalities, and ameliorate the clinical manifestations of BrS. Thus, resveratrol is potentially an inducer of AAV-mediated gene therapy for BrS.