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Magn Reson Med. 2005 Dec;54(6):1369-76.

Noninvasive monitoring of gene correction in dystrophic muscle.

Author information

  • 1Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida 32610, USA. glennw@phys.med.ufl.edu

Abstract

Gene and stem cell transfer have shown tremendous potential in rescuing dystrophic muscle in animal models. However, monitoring of gene transfer efficacy in clinical settings currently requires invasive muscle biopsies. We determined whether (1)H-magnetic resonance spectroscopy (MRS) and imaging (MRI) could be used to noninvasively monitor gene correction in dystrophic skeletal muscle. MRI/MRS measurements were performed in murine models of Limb Girdle (gammasg(-/-)) and Duchenne muscular dystrophy (mdx). Viral delivery of gammasg into gammasg(-/-) muscles was achieved using both an adenovirus and an adenoassociated virus. T(2)-weighted MRIs consistently revealed hyperintense regions in muscles of dystrophic mice, which agreed well with histologically determined damaged muscle fibers. (1)H-MRS revealed that the increase in T(2) in dystrophic muscle is not due to fatty tissue infiltration. Reintroduction of the gammasg gene in gammasg(-/-) muscles restored normal muscle histology, membrane stability, and T(2) contrast. Expression of gammasg also significantly decreased the number of pixels with increased T(2) values and MRI contrast agent uptake. Our data demonstrate that therapeutic correction of dystrophic lesions can be noninvasively monitored using endogenous MR contrast. This may be particularly relevant for future interventions in children with muscular dystrophy.

PMID:
16261578
[PubMed - indexed for MEDLINE]
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