Next Article in Journal
Silver Nanoparticles as Potential Antibacterial Agents
Next Article in Special Issue
Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection
Previous Article in Journal
Almond Skin Inhibits HSV-2 Replication in Peripheral Blood Mononuclear Cells by Modulating the Cytokine Network
Previous Article in Special Issue
Culture Conditions Affect Expression of DUX4 in FSHD Myoblasts
Open AccessReview

Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Leonidas A. Phylactou
Molecules 2015, 20(5), 8823-8855; https://doi.org/10.3390/molecules20058823
Received: 31 March 2015 / Revised: 8 May 2015 / Accepted: 11 May 2015 / Published: 15 May 2015
Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca2+) concentration, neuronal nitric oxide synthase (nNOS) localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca2+, nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart. View Full-Text
Keywords: heart; dystrophin; calcium; nNOS; mitochondria; utrophin up-regulation; read-through; viral gene therapy; cell-based therapy; exon skipping heart; dystrophin; calcium; nNOS; mitochondria; utrophin up-regulation; read-through; viral gene therapy; cell-based therapy; exon skipping
Show Figures

Graphical abstract

MDPI and ACS Style

Van Westering, T.L.E.; Betts, C.A.; Wood, M.J.A. Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy. Molecules 2015, 20, 8823-8855.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop