HDAC Inhibitors As Pharmacological Treatment for Duchenne Muscular Dystrophy: a Discovery Journey from Bench to Patients

Overview

Journal Trends Mol Med

Specialties General Medicine
Molecular Biology

Date 2024 Feb 26

PMID 38408879

Authors

Chiara Mozzetta

Vittorio Sartorelli

Christian Steinkuhler

Pier Lorenzo Puri

Affiliations

Soon will be listed here.

Abstract

Earlier evidence that targeting the balance between histone acetyltransferases (HATs) and deacetylases (HDACs), through exposure to HDAC inhibitors (HDACis), could enhance skeletal myogenesis, prompted interest in using HDACis to promote muscle regeneration. Further identification of constitutive HDAC activation in dystrophin-deficient muscles, caused by dysregulated nitric oxide (NO) signaling, provided the rationale for HDACi-based therapeutic interventions for Duchenne muscular dystrophy (DMD). In this review, we describe the molecular, preclinical, and clinical evidence supporting the efficacy of HDACis in countering disease progression by targeting pathogenic networks of gene expression in multiple muscle-resident cell types of patients with DMD. Given that givinostat is paving the way for HDACi-based interventions in DMD, next-generation HDACis with optimized therapeutic profiles and efficacy could be also explored for synergistic combinations with other therapeutic strategies.

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