Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

Allamand, Valérie; Donahue, Kathleen M.; Straub, Volker; Davisson, R L; Davidson, Beverly L.; Campbell, Kevin P.

doi:10.1038/sj.gt.3301247

Cited by 40 publications

(21 citation statements)

References 40 publications

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“…Together, these data demonstrate that the compromised sarcolemmal integrity in Sgcd-null mice can be reversed by restoration of the sarcoglycan complex. Similar results were previously obtained by using adenovirus-mediated ␣-SG gene transfer to ␣-SGdeficient mice (24).…”

Section: Resultssupporting

confidence: 79%

“…4a and 5 and data not shown). Injections into quadriceps femoris muscle resulted in transduction of vastus lateralis, but not rectus femoris (12,24) with an efficiency of transduction of Ϸ40-80% (Fig. 5 and data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown that the sarcoglycans can be restored at the sarcolemma after adenovirus mediated ␣-SG gene transfer to ␣-SG-deficient mice (24). However, it has remained untested whether gene transfer can target specialized muscle membranes and other cell-types within skeletal muscle.…”

Section: Resultsmentioning

confidence: 99%

“…To address this question, we injected recombinant ␤-or ␦-SG adenoviruses into corresponding null mice. We assumed that the inability of adenoviral particles to cross the perimysium (24), in which many arteries run, would prevent transduction of vascular smooth muscle. One single injection of ␤-or ␦-SG adenovirus into skeletal muscle of neonatal pups deficient in ␤-or ␦-SG, respectively, resulted in a complete restoration of the skeletal muscle DGC at the sarcolemma and prevented the dystrophic pathology.…”

Section: Discussionmentioning

confidence: 99%

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Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy

Durbeej

Sawatzki

Barresi

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Limb-girdle muscular dystrophy types 2E and F are characterized by skeletal muscle weakness and often cardiomyopathy and are due to mutations in the genes encoding ␤-and ␦-sarcoglycan. We previously demonstrated that loss of sarcoglycans in smooth muscle leads to constrictions of the microvasculature that contributes to the cardiac phenotype. It is unclear how vasculature abnormalities affect skeletal muscle. We injected recombinant ␤-or ␦-sarcoglycan adenoviruses into skeletal muscles of corresponding null mice. We hypothesized that the adenoviruses would not transduce vascular smooth muscle, and we would only target skeletal muscle. Indeed, sustained expression of intact sarcoglycansarcospan complex was noted at the sarcolemma, neuromuscular junction, myotendinous junction, and in peripheral nerve, but not in vascular smooth muscle. Gene transfer of the corresponding deleted sarcoglycan gene preserved sarcolemmal integrity, prevented pathological dystrophy and hypertrophy, and protected against exercised-induced damage. We conclude that vascular dysfunction is not a primary cause of ␤-and ␦-sarcoglycan-deficient muscular dystrophy. In addition, we show successful functional rescue of entire muscles after adenovirus-mediated gene delivery. Thus, virus-mediated gene transfer of sarcoglycans to skeletal muscle in combination with pharmacological prevention of cardiomyopathy constitute promising therapeutic strategies for limb-girdle muscular dystrophies.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy

Durbeej

Sawatzki

Barresi

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Another CA that binds reversibly to serum albumin, MS-325 (Epix Pharmaceuticals, Cambridge, MA, USA), has been used to detect chronic muscle lesions 34 and could be tested to evaluate acute muscle damage since its toxicity is negligible.…”

Section: Mntpps 4 and Necrosis Detectionmentioning

confidence: 99%

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

et al. 2005

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In vivo gene electrotransfer (ET) is a simple method of gene delivery in various tissues relying on the injection of plasmid DNA followed by application of electric pulses. Noninvasive tools are needed to evaluate the ET efficiency and the resulting tissue damages. In this study, we performed ET of rat tibialis muscle after injection of either a plasmid coding for luciferase or a contrast agent (CA) detected by using magnetic resonance imaging (MRI). Plasmid expression and CA intracellular trapped quantity were compared throughout the electric field intensity range 0-300 V/cm. Although the CA trapped quantity reflects only the electropermeabilization step, both measurements were correlated. MRI measurements gave easy access to tridimensional visualization of the labelled zones where the CA has been injected and the applied electric field had a value allowing permeabilization. We also performed MRI measurements of the water transverse relaxation time T2 as an indicator of tissue modification, and tested whether another CA specific for necrosis could be used to detect muscle necrosis at high electric field intensity. In conclusion, MRI measurements may bring multiparametric information upon the efficiency and tissue toxicity of an ET protocol by using a simple and safe CA.

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Cell–matrix interactions in muscle disease

Carmignac

Durbeej

2011

The Journal of Pathology

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The extracellular matrix (ECM) provides a solid scaffold and signals to cells through ECM receptors. The cell-matrix interactions are crucial for normal biological processes and when disrupted they may lead to pathological processes. In particular, the biological importance of ECM-cell membrane-cytoskeleton interactions in skeletal muscle is accentuated by the number of inherited muscle diseases caused by mutations in proteins conferring these interactions. In this review we introduce laminins, collagens, dystroglycan, integrins, dystrophin and sarcoglycans. Mutations in corresponding genes cause various forms of muscular dystrophy. The muscle disorders are presented as well as advances toward the development of treatment.

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Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

Cited by 40 publications

References 40 publications

Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy

Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

Cell–matrix interactions in muscle disease

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