Electrotransfer of the Full-Length Dog Dystrophin into Mouse and Dystrophic Dog Muscles

Pichavant, Christophe; Chapdelaine, Pierre; Cerri, Daniel Giuliano; Bizario, João C. S.; Tremblay, Jacques P.

doi:10.1089/hum.2010.024

Cited by 17 publications

(10 citation statements)

References 41 publications

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“…155,156 Dog FLDYS was also introduced with success in dystrophic dog muscle. 157 In this case, a specific immune response was observed in the treated dog muscle. Further studies are thus required to determine whether this immune response was against dystrophin or against the product of another transgene also present in the plasmid.…”

Section: Physical Approachmentioning

confidence: 62%

Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

Pichavant¹,

et al. 2011

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Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article.

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Section: Physical Approachmentioning

confidence: 62%

Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

Pichavant¹,

et al. 2011

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“…Hence, the primary goal of DMD gene therapy is to restore dystrophin expression. Many approaches have been tried, including gene replacement with plasmid (e.g., Myodys), advenovirus, and AAV vectors, gene repair with CRISPR editing, and exon-skipping with antisense oligonucleotides (188)(189)(190)(191)(192)(193).…”

Section: Therapeutic Testing In the Canine Model And Impact On Patienmentioning

confidence: 99%

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

et al. 2020

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Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer's disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials.

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“…[50][51][52] Limited expression and immune cell infiltration were observed following electrotransfer of canine dystrophin plasmids to GRMD muscle. 53,54 Adenovirus is the first viral vector used for delivering dystrophin to the canine muscle. Since the first-generation adenoviral vector has a packaging capacity of 8.2 kb, 55 investigators used a 6.2 kb, minimized dystrophin gene called the D17-48 minigene.…”

Section: Dystrophin Replacement Therapy In the Cdmd Modelmentioning

confidence: 99%

Duchenne muscular dystrophy gene therapy in the canine model

Duan¹

2015

Human Gene Therapy Clinical Development

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Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model.

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Electrotransfer of the Full-Length Dog Dystrophin into Mouse and Dystrophic Dog Muscles

Cited by 17 publications

References 41 publications

Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

Duchenne muscular dystrophy gene therapy in the canine model

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