Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate
Summary: Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribo...
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Elsevier
2019-11-01
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| Series: | JACC: Basic to Translational Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X19301913 |
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doaj-4212bb9493db490e828183607656df252020-11-25T02:17:17ZengElsevierJACC: Basic to Translational Science2452-302X2019-11-0147778791Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine TriphosphateStephen C. Kolwicz, Jr., PhD0John K. Hall, PhD1Farid Moussavi-Harami, MD2Xiolan Chen, PhD3Stephen D. Hauschka, PhD4Jeffrey S. Chamberlain, PhD5Michael Regnier, PhD6Guy L. Odom, PhD7Mitochondria and Metabolism Center, University of Washington, Seattle, WashingtonDepartment of Neurology, University of Washington, Seattle, WashingtonDivision of Cardiology, Department of Medicine, University of Washington, Seattle, WashingtonDepartment of Biochemistry, University of Washington, Seattle, Washington; Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, WashingtonDepartment of Biochemistry, University of Washington, Seattle, Washington; Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, WashingtonDepartment of Neurology, University of Washington, Seattle, Washington; Department of Biochemistry, University of Washington, Seattle, Washington; Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, WashingtonWellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington; Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Dr. Michael Regnier, Department of Bioengineering, University of Washington, 850 Republican Street, S180, Seattle, Washington 98109.Department of Neurology, University of Washington, Seattle, Washington; Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, Washington; Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Address for correspondence: Dr. Guy L. Odom, Department of Neurology, University of Washington, 850 Republican Street, S248, Box 358055, Seattle, Washington 98109.Summary: Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions. Cardiac-specific recombinant adeno-associated viral treatment of RNR holds therapeutic promise for improvement of cardiomyopathy in DMD patients. Key Words: cardiomyopathy, diastolic dysfunction, dystrophin, ribonucleotide reductase, recombinant adeno-associated virus vectorshttp://www.sciencedirect.com/science/article/pii/S2452302X19301913 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Stephen C. Kolwicz, Jr., PhD John K. Hall, PhD Farid Moussavi-Harami, MD Xiolan Chen, PhD Stephen D. Hauschka, PhD Jeffrey S. Chamberlain, PhD Michael Regnier, PhD Guy L. Odom, PhD |
| spellingShingle |
Stephen C. Kolwicz, Jr., PhD John K. Hall, PhD Farid Moussavi-Harami, MD Xiolan Chen, PhD Stephen D. Hauschka, PhD Jeffrey S. Chamberlain, PhD Michael Regnier, PhD Guy L. Odom, PhD Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate JACC: Basic to Translational Science |
| author_facet |
Stephen C. Kolwicz, Jr., PhD John K. Hall, PhD Farid Moussavi-Harami, MD Xiolan Chen, PhD Stephen D. Hauschka, PhD Jeffrey S. Chamberlain, PhD Michael Regnier, PhD Guy L. Odom, PhD |
| author_sort |
Stephen C. Kolwicz, Jr., PhD |
| title |
Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate |
| title_short |
Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate |
| title_full |
Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate |
| title_fullStr |
Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate |
| title_full_unstemmed |
Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate |
| title_sort |
gene therapy rescues cardiac dysfunction in duchenne muscular dystrophy mice by elevating cardiomyocyte deoxy-adenosine triphosphate |
| publisher |
Elsevier |
| series |
JACC: Basic to Translational Science |
| issn |
2452-302X |
| publishDate |
2019-11-01 |
| description |
Summary: Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions. Cardiac-specific recombinant adeno-associated viral treatment of RNR holds therapeutic promise for improvement of cardiomyopathy in DMD patients. Key Words: cardiomyopathy, diastolic dysfunction, dystrophin, ribonucleotide reductase, recombinant adeno-associated virus vectors |
| url |
http://www.sciencedirect.com/science/article/pii/S2452302X19301913 |
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