scholarly journals Forced Myofiber Regeneration Promotes Dystrophin Gene Transfer and Improved Muscle Function Despite Advanced Disease in Old Dystrophic Mice

2001 ◽  
Vol 4 (5) ◽  
pp. 499-507 ◽  
Author(s):  
Ghiabe H. Guibinga ◽  
Satoru Ebihara ◽  
Josephine Nalbantoglu ◽  
Paul Holland ◽  
George Karpati ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Muscle Function ◽  
Advanced Disease ◽  
Dystrophin Gene ◽  
Dystrophic Mice

Sustained Improvement of Muscle Function One Year After Full-Length Dystrophin Gene Transfer intomdxMice by a Gutted Helper-Dependent Adenoviral Vector

2004 ◽  
Vol 15 (2) ◽  
pp. 145-156 ◽  
Author(s):  
Roy W.R. Dudley ◽  
Yifan Lu ◽  
Rénald Gilbert ◽  
Stefan Matecki ◽  
Josephine Nalbantoglu ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Muscle Function ◽  
Adenoviral Vector ◽  
Dystrophin Gene ◽  
Full Length ◽  
Sustained Improvement ◽  
One Year

Novel Alternatives to Chemotherapy in Advanced Disease: Gene Transfer

2004 ◽  
pp. 99-120
Author(s):  
Paula Ghaneh ◽  
Christopher M. Halloran ◽  
Eithne Costello ◽  
John P. Neoptolemos
Keyword(s):  
Gene Transfer ◽  
Disease Gene ◽  
Advanced Disease

Differential effects of dystrophin and utrophin gene transfer in immunocompetent muscular dystrophy (mdx) mice

2000 ◽  
Vol 3 (3) ◽  
pp. 133-144 ◽  
Author(s):  
SATORU EBIHARA ◽  
GHIABE-HENRI GUIBINGA ◽  
RENALD GILBERT ◽  
JOSEPHINE NALBANTOGLU ◽  
BERNARD MASSIE ◽  
...  
Keyword(s):  
Immune System ◽  
Muscular Dystrophy ◽  
Gene Transfer ◽  
Tibialis Anterior Muscle ◽  
High Stress ◽  
Dystrophin Gene ◽  
Foreign Protein ◽  
Mdx Mice ◽  
Host Immune System ◽  
Differential Effects

Ebihara, Satoru, Ghiabe-Henri Guibinga, Renald Gilbert, Josephine Nalbantoglu, Bernard Massie, George Karpati, and Basil J. Petrof. Differential effects of dystrophin and utrophin gene transfer in immunocompetent muscular dystrophy (mdx) mice. Physiol Genomics 3: 133–144, 2000.—Duchenne muscular dystrophy (DMD) is a fatal disease caused by defects in the gene encoding dystrophin. Dystrophin is a cytoskeletal protein, which together with its associated protein complex, helps to protect the sarcolemma from mechanical stresses associated with muscle contraction. Gene therapy efforts aimed at supplying a normal dystrophin gene to DMD muscles could be hampered by host immune system recognition of dystrophin as a “foreign” protein. In contrast, a closely related protein called utrophin is not foreign to DMD patients and is able to compensate for dystrophin deficiency when overexpressed throughout development in transgenic mice. However, the issue of which of the two candidate molecules is superior for DMD therapy has remained an open question. In this study, dystrophin and utrophin gene transfer effects on dystrophic muscle function were directly compared in the murine (mdx) model of DMD using E1/E3-deleted adenovirus vectors containing either a dystrophin (AdV-Dys) or a utrophin (AdV-Utr) transgene. In immunologically immature neonatal animals, AdV-Dys and AdV-Utr improved tibialis anterior muscle histopathology, force-generating capacity, and the ability to resist injury caused by high-stress contractions to an equivalent degree. By contrast, only AdV-Utr was able to achieve significant improvement in force generation and the ability to resist stress-induced injury in the soleus muscle of immunocompetent mature mdx animals. In addition, in mature mdx mice, there was significantly greater transgene persistence and reduced inflammation with utrophin compared to dystrophin gene transfer. We conclude that dystrophin and utrophin are largely equivalent in their intrinsic abilities to prevent the development of muscle necrosis and weakness when expressed in neonatal mdx animals with an immature immune system. However, because immunity against dystrophin places an important limitation on the efficacy of dystrophin gene replacement in an immunocompetent mature host, the use of utrophin as an alternative to dystrophin gene transfer in this setting appears to offer a significant therapeutic advantage.

scholarly journals AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice

JCI Insight ◽  
2018 ◽  
Vol 3 (23) ◽  
Author(s):  
Chady H. Hakim ◽  
Nalinda B. Wasala ◽  
Christopher E. Nelson ◽  
Lakmini P. Wasala ◽  
Yongping Yue ◽  
...  
Keyword(s):  
Muscle Function ◽  
Dystrophic Mice

scholarly journals Chronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20856 ◽  
Author(s):  
Lawrence T. Bish ◽  
Mark Yarchoan ◽  
Meg M. Sleeper ◽  
Jeffrey A. Gazzara ◽  
Kevin J. Morine ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Dystrophic Mice

Human dystrophin gene transfer: production and expression of a functional recombinant DNA-based gene

1991 ◽  
Vol 88 (1) ◽  
pp. 53-58 ◽  
Author(s):  
George Dickson ◽  
DonaldR. Love ◽  
KayE. Davies ◽  
KirmE. Wells ◽  
TonyA. Piper ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Recombinant Dna ◽  
Dystrophin Gene ◽  
Human Dystrophin

scholarly journals Female Outperformance in Voluntary Running Persists in Dystrophin-Null and Klotho-Overexpressing Mice

2021 ◽  
pp. 1-11
Author(s):  
Michael Phelps ◽  
Zipora Yablonka-Reuveni
Keyword(s):  
Wheel Running ◽  
Dystrophin Gene ◽  
Muscle Disease ◽  
Mouse Strains ◽  
Male Mice ◽  
Wild Type ◽  
Running Performance ◽  
Voluntary Running ◽  
And Function ◽  
Dystrophic Mice

Background: Duchenne muscular dystrophy is a degenerative muscle disease that results from impairment of the dystrophin gene. The disease causes progressive loss in muscle mass and function. Objective: The anti-aging protein, α-klotho, has been implicated in the regulation of muscle regeneration. We previously discovered that mice harboring reduced α-klotho levels exhibited a decline in muscle strength and running endurance. Method: To investigate the ability of α-klotho to improve overall endurance in a dystrophin null murine model, we examined the voluntary wheel running performance of dystrophin-null, mdx4cv mice overexpressing an α-klotho transgene. Results: As expected, compared to wild type, both male and female dystrophic mice exhibited reduced running ability that was characterized by shorter running duration and longer periods of rest between cycles of activity. While our results did not detect an improvement in running performance with α-klotho overexpression, we identified distinct differences in the running patterns between females and males from all mouse strains analyzed (i.e., mdx4cv, mdx4cv overexpressing α-klotho, α-klotho overexpressing, α-klotho hypomorph, and wild type). For all strains, male mice displayed significantly reduced voluntary running ability compared to females. Further analysis of the mdx4cv strains demonstrated that male mice ran for shorter lengths of time and took longer breaks. However, we did not identify gender-associated differences in the actual speed at which mdx4cv mice ran. Conclusion: Our data suggest key differences in the running capabilities of female and male mice, which are of particularly relevant to studies of dystrophin-null mice.

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