The almost complete loss of dystrophin isoform Dp427 causes a multi-system pathology that features in addition to skeletal muscle weakness also late-onset cardio-respiratory deficiencies, impaired metabolism and abnormalities in the central nervous system.
DMD is a devastating inherited X-linked muscle disease characterized by progressive muscle weakness due to lack of dystrophin expression in muscle fiber sarcolemma.<sup>1</sup> Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin, this approach has been hindered by limited survival (less than 1%) of the injected cells.<sup>1</sup> The fact that 99% of the cells were not surviving implantation was seen as a major weakness with this technology by most.
Dystrophin deficiency clinically manifests as skeletal and cardiac muscle weakness, leading to muscle wasting and premature death due to cardiac and respiratory failure.Currently, no cure exists.
Duchenne muscular dystrophy (DMD), caused by the absence of the protein dystrophin, is characterized as a neuromuscular disease in which muscle weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology.
This case suggests that very low levels of DMD exon skipping and dystrophin protein expression may result in amelioration of skeletal muscle weakness, a finding relevant to current dystrophin-restoring therapies.
Duchenne muscular dystrophy (DMD) affects 1:3500-1:5000 male births, and is caused by X-linked mutations in the dystrophin gene, manifested by progressive muscle weakness and wasting due to the absence of dystrophin protein, leading to degeneration of skeletal muscle.
This technology has been tested in paralysed patients, such as those with cervical spinal cord injuries or amyotrophic lateral sclerosis, but it has not been tested systematically in Duchenne muscular dystrophy (DMD), which is a severe type of muscular dystrophy due to the loss of dystrophin and is often accompanied by progressive muscle weakness and wasting.
Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked recessive neuromuscular disorders characterized by progressive irreversible muscle weakness and atrophy that affect both skeletal and cardiac muscles.
A novel class of AONs made of tricyclo-DNA (tcDNA) is considered very promising for the treatment of Duchenne muscular dystrophy (DMD), a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment.
Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone.
For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology.
Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness.
It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle.
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle.
Although longer term studies are needed to clarify the relationship between dystrophin restoration following therapeutic intervention and the level of circulating miRNAs, our results indicate that miR-1 and miR-133 can be considered as exploratory biomarkers for monitoring the progression of muscle weakness and indirectly the remaining muscle mass in DMD.
Eighteen females showing a mosaic pattern of dystrophin expression on muscle biopsy were recruited and classified as symptomatic (7) or asymptomatic (11), based on the presence or absence of muscle weakness.
Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD).
We report here a case of dystrophinopathy in a 9-years-old boy with a 2-bp deletion in exon 74 of the dystrophin gene; however, the boy had no clear clinical signs of muscle weakness.