NBD delivery improves the disease phenotype of the golden retriever model of Duchenne muscular dystrophy
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Kornegay, Joe N, et al. Nbd Delivery Improves the Disease Phenotype of the Golden Retriever Model of Duchenne Muscular Dystrophy. BioMed Central, 2014. https://doi.org/10.17615/30r7-6b57APA
Kornegay, J., Peterson, J., Bogan, D., Kline, W., Bogan, J., Dow, J., Fan, Z., Wang, J., Ahn, M., Zhu, H., Styner, M., & Guttridge, D. (2014). NBD delivery improves the disease phenotype of the golden retriever model of Duchenne muscular dystrophy. BioMed Central. https://doi.org/10.17615/30r7-6b57Chicago
Kornegay, Joe N., Jennifer M Peterson, Daniel J Bogan, William Kline, Janet R Bogan, Jennifer L Dow, Zheng Fan et al. 2014. Nbd Delivery Improves the Disease Phenotype of the Golden Retriever Model of Duchenne Muscular Dystrophy. BioMed Central. https://doi.org/10.17615/30r7-6b57- Creator
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Kornegay, Joe N.
- Affiliation: School of Medicine, Gene Therapy Center
- Other Affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, USA
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Peterson, Jennifer M
- Other Affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, USA
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Bogan, Daniel J
- Affiliation: School of Medicine, Gene Therapy Center
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Kline, William
- Other Affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, USA
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Bogan, Janet R
- Affiliation: School of Medicine, Gene Therapy Center
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Dow, Jennifer L
- Affiliation: School of Medicine, Gene Therapy Center
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Fan, Zheng
- Affiliation: School of Medicine, Department of Neurology
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Wang, Jiahui
- Affiliation: School of Medicine, Department of Psychiatry
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Ahn, Mihye
- Affiliation: Gillings School of Global Public Health, Department of Biostatistics
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Zhu, Hongtu
- Affiliation: Gillings School of Global Public Health, Department of Biostatistics
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Styner, Martin
- Affiliation: College of Arts and Sciences, Department of Computer Science
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Guttridge, Denis C
- Other Affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, USA; The Ohio State University College of Medicine, Columbus, USA
- Abstract
- Abstract Background Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene and afflicts skeletal and cardiac muscles. Previous studies showed that DMD is associated with constitutive activation of NF-κB, and in dystrophin-deficient mdx and utrophin/dystrophin (utrn -/- ;mdx) double knock out (dko) mouse models, inhibition of NF-κB with the Nemo Binding Domain (NBD) peptide led to significant improvements in both diaphragm and cardiac muscle function. Methods A trial in golden retriever muscular dystrophy (GRMD) canine model of DMD was initiated with four primary outcomes: skeletal muscle function, MRI of pelvic limb muscles, histopathologic features of skeletal muscles, and safety. GRMD and wild type dogs at 2 months of age were treated for 4 months with NBD by intravenous infusions. Results were compared with those collected from untreated GRMD and wild type dogs through a separate, natural history study. Results Results showed that intravenous delivery of NBD in GRMD dogs led to a recovery of pelvic limb muscle force and improvement of histopathologic lesions. In addition, NBD-treated GRMD dogs had normalized postural changes and a trend towards lower tissue injury on magnetic resonance imaging. Despite this phenotypic improvement, NBD administration over time led to infusion reactions and an immune response in both treated GRMD and wild type dogs. Conclusions This GRMD trial was beneficial both in providing evidence that NBD is efficacious in a large animal DMD model and in identifying potential safety concerns that will be informative moving forward with human trials.
- Date of publication
- October 23, 2014
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Kornegay et al.; licensee BioMed Central Ltd.
- Language
- English
- Bibliographic citation
- Skeletal Muscle. 2014 Oct 23;4(1):18
- Publisher
- BioMed Central
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