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Noninvasive monitoring of gene correction in dystrophic muscle
Author(s) -
Walter Glenn,
Cordier Laurence,
Bloy Dorothy,
Lee Sweeney H.
Publication year - 2005
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.20721
Subject(s) - duchenne muscular dystrophy , muscular dystrophy , magnetic resonance imaging , skeletal muscle , pathology , mdx mouse , genetic enhancement , histology , medicine , biology , anatomy , dystrophin , gene , radiology , biochemistry
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 (γsg −/− ) and Duchenne muscular dystrophy ( mdx ). Viral delivery of γsg into γsg −/− 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 γsg gene in γsg −/− muscles restored normal muscle histology, membrane stability, and T 2 contrast. Expression of γsg 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. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.