A promising therapeutic approach deals with functional substitution of dystrophin by utrophin, a structural homolog that might be able to compensate dystrophin absence in DMD muscle fibers.
Here, we report one of the largest study based on the comparison of clinical, cognitive, molecular and expression data in a large cohort of 81 patients affected with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) bearing mutations predicted to affect either all dystrophin products, including Dp71 or all dystrophin products, except Dp71.
Here we present the first report of failure of isolation of nonsense dystrophin mRNA in lymphocytes but success in skeletal muscle in a female carrier of DMD.
Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin-deficient mouse model of Duchenne muscular dystrophy.
To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD.
Therefore, these data suggest that S48168/ARM210 may be a safe therapeutic option, at the dose levels tested, for the treatment of Duchenne muscular dystrophy (DMD).-Capogrosso, R. F., Mantuano, P., Uaesoontrachoon, K., Cozzoli, A., Giustino, A., Dow, T., Srinivassane, S., Filipovic, M., Bell, C., Vandermeulen, J., Massari, A. M., De Bellis, M., Conte, E., Pierno, S., Camerino, G. M., Liantonio, A., Nagaraju, K., De Luca, A. Ryanodine channel complex stabilizer compound S48168/ARM210 as a disease modifier in dystrophin-deficient mdx mice: proof-of-concept study and independent validation of efficacy.
A retrospective single institution long-term follow-up study was carried out in DMD patients with both complete lack of muscle dystrophin and genotyping.
These results suggest that the reduction of Dp71 protein in the Duchenne muscular dystrophy neurons leads to alterations in SERCA2 and to elevated cytosolic Ca<sup>2+</sup> concentration with consequent potential disruption of the dystrophin proteins and Dp71-associated proteins.
Since the donor of one of these biopsies has a large deletion of the 5'-region of the DMD gene, our results argue against the recent proposal that nebulin is the gene mutated in DMD.
Detection of the causative DMD variant and determination of its effects on dystrophin expression is best achieved by analysis of RNA extracted from muscle biopsy material.
Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene.
Duchenne muscular dystrophy (DMD) results from genetic mutations of the gene encoding dystrophin, leading to muscle inflammation and degeneration that is typically treated with glucocorticoids.
Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation.
The human pluripotent stem cells included the WT embryonic line CCTL14 and the induced dystrophin deficient line reprogrammed from fibroblasts of a patient affected by Duchenne Muscular Dystrophy (DMD, complete loss of dystrophin expression).
Experiments in dystrophin gene transgenic mice have supported the concept of treating Duchenne muscular dystrophy (DMD) by demonstrating that regional expression of recombinant dystrophin in dystrophic muscle leads to regional restoration of normal muscle morphology and that dystrophin mini-genes driven by muscle specific regulatory elements are probably more effective than the full-length dystrophin gene.
Using antisense oligonucleotides (AONs), the disrupted DMD reading frame is restored, allowing generation of partially functional dystrophin and conversion of a severe Duchenne into a milder Becker muscular dystrophy phenotype.
In the Duchenne muscular dystrophy (DMD) syndrome, mutations affecting expression of Dp71, the main dystrophin isoform of the multipromoter dmd gene in brain, have been associated with intellectual disability and neuropsychiatric disturbances.
DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with mutations in the distal part of the DMD gene, predicted to affect expression of shorter protein isoforms.