Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.
JACC Basic Transl Sci
; 4(7): 778-791, 2019 Nov.
Article
en En
| MEDLINE
| ID: mdl-31998848
ABSTRACT
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.
CK8, miniaturized murine creatine kinase regulatory cassette; CMV, cytomegalovirus; DMD, Duchenne muscular dystrophy; RNR, ribonucleotide reductase; cTnT, cardiac troponin T; cardiomyopathy; dADP, deoxy-adenosine diphosphate; dATP, deoxy-adenosine triphosphate; diastolic dysfunction; dystrophin; mdx, mouse muscular dystrophy model; rAAV, recombinant adeno-associated viral vector; recombinant adeno-associated virus vectors; ribonucleotide reductase; µDys, microdystrophin
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
JACC Basic Transl Sci
Año:
2019
Tipo del documento:
Article