Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy.

Autor:	Filareto A; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305.; Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 90304., Maguire-Nguyen K; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305.; Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 90304., Gan Q; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305., Aldanondo G; Neuroscience Area, Biodonostia Research Institute, 20014 San Sebastian, Spain., Machado L; Faculte de Medecine, Universite Paris Est Creteil, 94000 Creteil, France., Chamberlain JS; Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington School of Medicine, Seattle, WA 98195., Rando TA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305; rando@stanford.edu.; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305.; Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 90304.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jul 24; Vol. 115 (30), pp. 7741-7746. Date of Electronic Publication: 2018 Jul 09.
DOI:	10.1073/pnas.1802425115
Abstrakt:	Duchenne muscular dystrophy (DMD) is a rare, muscle degenerative disease resulting from the absence of the dystrophin protein. DMD is characterized by progressive loss of muscle fibers, muscle weakness, and eventually loss of ambulation and premature death. Currently, there is no cure for DMD and improved methods of disease monitoring are crucial for the development of novel treatments. In this study, we describe a new method of assessing disease progression noninvasively in the mdx model of DMD. The reporter mice, which we term the dystrophic Degeneration Reporter strains, contain an inducible CRE-responsive luciferase reporter active in mature myofibers. In these mice, muscle degeneration is reflected in changes in the level of luciferase expression, which can be monitored using noninvasive, bioluminescence imaging. We monitored the natural history and disease progression in these dystrophic report mice and found that decreases in luciferase signals directly correlated with muscle degeneration. We further demonstrated that this reporter strain, as well as a previously reported Regeneration Reporter strain, successfully reveals the effectiveness of a gene therapy treatment following systemic administration of a recombinant adeno-associated virus-6 (rAAV-6) encoding a microdystrophin construct. Our data demonstrate the value of these noninvasive imaging modalities for monitoring disease progression and response to therapy in mouse models of muscular dystrophy. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu