Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease arising from defects in the dystrophin gene, typically nonsense or frameshift mutations, that preclude the synthesis of a functional protein. A milder, allelic version of the disease, Becker muscular dystrophy, generally arises from in-frame deletions that allow synthesis of a shorter but still semifunctional protein. Therapie...

Duchenne muscular dystrophy (DMD) is an X-linked, lethal disease caused by mutations of the dystrophin gene. No effective therapy is available, but dystrophin gene transfer to skeletal muscle has been proposed as a treatment for DMD. We have developed a strategy for efficient in vivo gene transfer of dystrophin cDNA into regenerating skeletal muscle. Retroviral producer cells, which release a v...

Duchenne Muscular Dystrophy (DMD) is a genetic disorder involving progressive muscle deterioration leading to loss of mobility, cardiomyopathy, and respiratory complications an early death by the fourth decade life. Males are affected more often as DMD results from mutation in dystrophin gene residing on X chromosome. The complete functional lack dystrophin, which culminates inadequate connecti...

NEW FINDINGS What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. Th...

BACKGROUND Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy often result from deletion mutations in the dystrophin gene that may lead to expression of an altered dystrophin protein in cardiac muscle. Cardiac involvement is present in approximately 70% of BMD and all X-linked dilated cardiomyopathy cases. To date, the timing of cardiomyopathy development remains unpredictable....

A subset of patients harboring mutations in the dystrophin gene suffer from X-linked dilated cardiomyopathy (XLCM), a familial heart disease that is not accompanied by any clinical signs of skeletal muscle myopathy. As the muscle (M) isoform of dystrophin is not expressed in these patients, the absence of skeletal muscle symptoms has been attributed to expression of the brain (B) and cerebellar...

Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic ...

Heart failure in children and adults is often the consequence of myocarditis associated with Coxsackievirus (CV) infection. Upon CV infection, enteroviral protease 2A cleaves a small number of host proteins including dystrophin, which links actin filaments to the plasma membrane of muscle fiber cells (sarcolemma). It is unknown whether protease 2A-mediated cleavage of dystrophin and subsequent ...

We report a 4-yr and 5-month-old boy with severe clinical features of an early-onset Duchenne muscular dystrophy, who had a very short (110 kDa) dystrophin at the sarcolemma. The patient had a large deletion (exons 2-44) of the dystrophin gene which was predicted to cause a reading frame shift. Sequence analysis of dystrophin mRNA in muscle revealed an alternatively spliced gene product from ex...

Cardiomyopathy is often found in patients with Duchenne and Becker muscular dystrophy, which are X linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects present in many different ways and cases of mild Becker muscular dystrophy have been described in which cardiomyopathy was severe. Female carriers of Duchenne muscular dystrophy can develop symptomatic skeletal m...