scholarly journals Correction of Dystrophin Expression in Cells From Duchenne Muscular Dystrophy Patients Through Genomic Excision of Exon 51 by Zinc Finger Nucleases

2015 ◽  
Vol 23 (3) ◽  
pp. 523-532 ◽  
Author(s):  
David G Ousterout ◽  
Ami M Kabadi ◽  
Pratiksha I Thakore ◽  
Pablo Perez-Pinera ◽  
Matthew T Brown ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Zinc Finger ◽  
Zinc Finger Nucleases ◽  
Dystrophin Expression ◽  
In Cells

scholarly journals Reading Frame Correction by Targeted Genome Editing Restores Dystrophin Expression in Cells From Duchenne Muscular Dystrophy Patients

2013 ◽  
Vol 21 (9) ◽  
pp. 1718-1726 ◽  
Author(s):  
David G Ousterout ◽  
Pablo Perez-Pinera ◽  
Pratiksha I Thakore ◽  
Ami M Kabadi ◽  
Matthew T Brown ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Genome Editing ◽  
Reading Frame ◽  
Dystrophin Expression ◽  
In Cells

scholarly journals Restoring Dystrophin Expression in Duchenne Muscular Dystrophy Muscle

2011 ◽  
Vol 179 (1) ◽  
pp. 12-22 ◽  
Author(s):  
Eric P. Hoffman ◽  
Abby Bronson ◽  
Arthur A. Levin ◽  
Shin'ichi Takeda ◽  
Toshifumi Yokota ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dystrophin Expression

Eteplirsen treatment for Duchenne muscular dystrophy

Neurology ◽  
2018 ◽  
Vol 90 (24) ◽  
pp. e2146-e2154 ◽  
Author(s):  
Jay S. Charleston ◽  
Frederick J. Schnell ◽  
Johannes Dworzak ◽  
Cas Donoghue ◽  
Sarah Lewis ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Western Blot ◽  
Reverse Transcription ◽  
Exon Skipping ◽  
Fold Increase ◽  
Cell Penetration ◽  
Reverse Transcription Pcr ◽  
Dystrophin Expression ◽  
Immunofluorescence Intensity

ObjectiveTo describe the quantification of novel dystrophin production in patients with Duchenne muscular dystrophy (DMD) after long-term treatment with eteplirsen.MethodsClinical study 202 was an observational, open-label extension of the randomized, controlled study 201 assessing the safety and efficacy of eteplirsen in patients with DMD with a confirmed mutation in the DMD gene amenable to correction by skipping of exon 51. Patients received once-weekly IV doses of eteplirsen 30 or 50 mg/kg. Upper extremity muscle biopsy samples were collected at combined study week 180, blinded, and assessed for dystrophin-related content by Western blot, Bioquant software measurement of dystrophin-associated immunofluorescence intensity, and percent dystrophin-positive fibers (PDPF). Results were contrasted with matched untreated biopsies from patients with DMD. Reverse transcription PCR followed by Sanger sequencing of newly formed slice junctions was used to confirm the mechanism of action of eteplirsen.ResultsReverse transcription PCR analysis and sequencing of the newly formed splice junction confirmed that 100% of treated patients displayed the expected skipped exon 51 sequence. In treated patients vs untreated controls, Western blot analysis of dystrophin content demonstrated an 11.6-fold increase (p = 0.007), and PDPF analysis demonstrated a 7.4-fold increase (p < 0.001). The PDPF findings were confirmed in a re-examination of the sample (15.5-fold increase, p < 0.001). Dystrophin immunofluorescence intensity was 2.4-fold greater in treated patients than in untreated controls (p < 0.001).ConclusionTaken together, the 4 assays, each based on unique evaluation mechanisms, provided evidence of eteplirsen muscle cell penetration, exon skipping, and induction of novel dystrophin expression.Classification of evidenceThis study provides Class II evidence of the muscle cell penetration, exon skipping, and induction of novel dystrophin expression by eteplirsen, as confirmed by 4 assays.

scholarly journals A Simplified Immune Suppression Scheme Leads to Persistent Micro-dystrophin Expression in Duchenne Muscular Dystrophy Dogs

2012 ◽  
Vol 23 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Jin-Hong Shin ◽  
Yongping Yue ◽  
Arun Srivastava ◽  
Bruce Smith ◽  
Yi Lai ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Immune Suppression ◽  
Dystrophin Expression

P.20.12 Gene therapy of Duchenne Muscular Dystrophy using rAAV vectors: Patterns of dystrophin expression and histological improvements

2013 ◽  
Vol 23 (9-10) ◽  
pp. 842
Author(s):  
Y. Cherel ◽  
C. Le Guiner ◽  
L. Guigand ◽  
M. Dutilleul ◽  
T. Larcher ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dystrophin Expression
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