Research Articles

All-Cause Mortality and Cardiovascular Outcomes With Prophylactic Steroid Therapy in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) patients suffer from cardiorespiratory complications in which progressive respiratory failure is the most common cause of mortality, and cardiomyopathy accounts for 20%-40% of all deaths. Inhibitors of the renin-angiotensin-aldosterone system (with or without beta blockers) are used clinically to delay progressive ventricular dysfunction.

Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy

The use of antisense oligonucleotides (AON) to induce exon skipping in precursor mRNA is at the forefront of clinical research for the treatment of DMD. The most advanced programs from Sarepta Therapeutics and GSK/Prosensa target exon 51, and are currently in Phase II and Phase III clinical trails in the US and the rest of the world. Their approval is anticipated within the near future.

Strategies that could enhance or improve the efficiency of the current (and future) exon skipping drugs to produce novel dystrophin have been sought by a number of research groups over the last few years. Now a recent report by Kendall et al. describes the identification of a compound that enhances the efficiency of exon skipping in vitro and in vivo. The compound, the approved drug Dantrolene, works in concert with the exon skipping drug to restore dystrophin levels in the mdxmice and also in reprogrammed myotubes from DMD patients. This research offers insight into the exon skipping process, and could provide a fast track opportunity to use an approved drug to enhance the efficiency of current exon skipping drugs in future clinical trials.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

A recent placebo-controlled clinical study on the effects of the PDE5A inhibitor drug Tadalafil (Cialis), demonstrated beneficial effects on muscle blood flow in a model of muscle ischemia in men with Becker muscular dystrophy who harbor a mutation in which the neuronal nitric oxide synthase is absent. The result reinforce earlier findings in mice and Duchene patients and highlight the role of this pathway in muscle homeostasis.

Sarepta Therapeutics Announces Significant Clinical Benefit With Eteplirsen After 36 Weeks in Phase IIb Study for the Treatment of Duchenne Muscular Dystrophy

Sarepta Therapeutics (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced that treatment with its exon-skipping compound, eteplirsen, achieved a significant clinical benefit on the primary clinical outcome, the 6-minute walk test (6MWT), over a placebo/delayed treatment cohort in a Phase IIb trial in Duchenne muscular dystrophy (DMD) patients.

Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database.

A recent paper from Elisabeth Rumeur and colleagues ( introduces a new database ( that is made freely available for public access. It contains information from 945 clinical reports.

The eDystrophin database compliments two other databases of DMD human mutations: the Leiden Muscular Dystrophy database and the UMD-DMD French database. The eDystrophin database is specifically dedicated to providing information about in-frame mutations (deletions, duplications and substitutions) of the DMD gene and the consequences of these alterations from a clinical perspective and a protein structure perspective.
The database is user friendly and informative and should be a source of much needed information for researchers, parents and patients alike.

Inhibiting myostatin reverses muscle fibrosis through apoptosis.

Myostatin is both a regulator of muscle growth and a stimulator of muscle fibroblasts to proliferate; and there is an accumulating body of evidence that demonstrates inhibition of myostatin/ActRIIB signaling can ameliorate the pathology and function of dystrophic muscle in preclinical models of Duchene muscular dystrophy.