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Multiple muscles in the AMD quail can be "cross-corrected" of pathologic glycogen accumulation after intravenous injection of an [E1-, polymerase-] adenovirus vector encoding human acid-alpha-glucosidase.
J Gene Med. 2003 May; 5(5):399-406.JG

Abstract

BACKGROUND

Previously, in murine models of acid maltase deficiency (AMD), we demonstrated that intravenous administration of an improved adenovirus (Ad) vector encoding human acid alpha glucosidase (hGAA) resulted in liver transduction, followed by high-level hepatocyte-mediated secretion of hGAA into the plasma space. The hGAA secreted by the liver was taken up and targeted to muscle cell lysosomes. The levels of hGAA achieved by this approach resulted in clearance of lysosomal glycogen accumulations; in some muscle tissues the effect was prolonged (>6 months). We next wished to demonstrate whether this approach could be generalized across divergent species. To accomplish this goal, we determined whether a similar approach would also result in efficacy, but in a quail model of AMD.

METHODS

An [E1-, E2b-]Ad vector encoding hGAA was intravenously injected into AMD quails. At several time points thereafter, plasma, liver, and multiple muscle tissues were assayed for evidence of hGAA gene expression, liver-mediated hGAA secretion, uptake of hGAA by skeletal muscles, and evidence of glycogen correction in AMD skeletal muscles. These results were compared with those obtained from mock-injected AMD or wild-type quails.

RESULTS

Intravenous [E1-, E2b-]Ad/hGAA vector injection resulted in high-level liver transduction and hepatic secretion of precursor forms of hGAA. The hepatically secreted hGAA was found to not only be efficiently taken up by cardiac and skeletal muscles, but was also proteolytically cleaved and processed equivalently to the quail-GAA protein detected in wild-type quails. The observations suggest that the signals regulating muscle cell uptake (but not proteolytic cleavage) of lysosomal enzymes are conserved and recognized across divergent species of vertebrates. Importantly, once localized to skeletal muscle lysosomes, the hGAA was able to effectively clear the glycogen accumulations present in AMD quail muscles.

CONCLUSIONS

Adenovirus-mediated transduction of the hGAA gene, followed by hepatic secretion, uptake, and cross-correction of the pathologic glycogen accumulation noted in multiple muscles of both the AMD mouse and AMD quail, adds support to the notion that gene transfer strategies (Ad-mediated or other agents) targeting liver tissues with the hGAA gene are likely to be highly efficacious in humans affected by AMD.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12731088

Citation

McVie-Wylie, A J., et al. "Multiple Muscles in the AMD Quail Can Be "cross-corrected" of Pathologic Glycogen Accumulation After Intravenous Injection of an [E1-, Polymerase-] Adenovirus Vector Encoding Human Acid-alpha-glucosidase." The Journal of Gene Medicine, vol. 5, no. 5, 2003, pp. 399-406.
McVie-Wylie AJ, Ding EY, Lawson T, et al. Multiple muscles in the AMD quail can be "cross-corrected" of pathologic glycogen accumulation after intravenous injection of an [E1-, polymerase-] adenovirus vector encoding human acid-alpha-glucosidase. J Gene Med. 2003;5(5):399-406.
McVie-Wylie, A. J., Ding, E. Y., Lawson, T., Serra, D., Migone, F. K., Pressley, D., Mizutani, M., Kikuchi, T., Chen, Y. T., & Amalfitano, A. (2003). Multiple muscles in the AMD quail can be "cross-corrected" of pathologic glycogen accumulation after intravenous injection of an [E1-, polymerase-] adenovirus vector encoding human acid-alpha-glucosidase. The Journal of Gene Medicine, 5(5), 399-406.
McVie-Wylie AJ, et al. Multiple Muscles in the AMD Quail Can Be "cross-corrected" of Pathologic Glycogen Accumulation After Intravenous Injection of an [E1-, Polymerase-] Adenovirus Vector Encoding Human Acid-alpha-glucosidase. J Gene Med. 2003;5(5):399-406. PubMed PMID: 12731088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple muscles in the AMD quail can be "cross-corrected" of pathologic glycogen accumulation after intravenous injection of an [E1-, polymerase-] adenovirus vector encoding human acid-alpha-glucosidase. AU - McVie-Wylie,A J, AU - Ding,E Y, AU - Lawson,T, AU - Serra,D, AU - Migone,F K, AU - Pressley,D, AU - Mizutani,M, AU - Kikuchi,T, AU - Chen,Y T, AU - Amalfitano,A, PY - 2003/5/6/pubmed PY - 2004/2/11/medline PY - 2003/5/6/entrez SP - 399 EP - 406 JF - The journal of gene medicine JO - J Gene Med VL - 5 IS - 5 N2 - BACKGROUND: Previously, in murine models of acid maltase deficiency (AMD), we demonstrated that intravenous administration of an improved adenovirus (Ad) vector encoding human acid alpha glucosidase (hGAA) resulted in liver transduction, followed by high-level hepatocyte-mediated secretion of hGAA into the plasma space. The hGAA secreted by the liver was taken up and targeted to muscle cell lysosomes. The levels of hGAA achieved by this approach resulted in clearance of lysosomal glycogen accumulations; in some muscle tissues the effect was prolonged (>6 months). We next wished to demonstrate whether this approach could be generalized across divergent species. To accomplish this goal, we determined whether a similar approach would also result in efficacy, but in a quail model of AMD. METHODS: An [E1-, E2b-]Ad vector encoding hGAA was intravenously injected into AMD quails. At several time points thereafter, plasma, liver, and multiple muscle tissues were assayed for evidence of hGAA gene expression, liver-mediated hGAA secretion, uptake of hGAA by skeletal muscles, and evidence of glycogen correction in AMD skeletal muscles. These results were compared with those obtained from mock-injected AMD or wild-type quails. RESULTS: Intravenous [E1-, E2b-]Ad/hGAA vector injection resulted in high-level liver transduction and hepatic secretion of precursor forms of hGAA. The hepatically secreted hGAA was found to not only be efficiently taken up by cardiac and skeletal muscles, but was also proteolytically cleaved and processed equivalently to the quail-GAA protein detected in wild-type quails. The observations suggest that the signals regulating muscle cell uptake (but not proteolytic cleavage) of lysosomal enzymes are conserved and recognized across divergent species of vertebrates. Importantly, once localized to skeletal muscle lysosomes, the hGAA was able to effectively clear the glycogen accumulations present in AMD quail muscles. CONCLUSIONS: Adenovirus-mediated transduction of the hGAA gene, followed by hepatic secretion, uptake, and cross-correction of the pathologic glycogen accumulation noted in multiple muscles of both the AMD mouse and AMD quail, adds support to the notion that gene transfer strategies (Ad-mediated or other agents) targeting liver tissues with the hGAA gene are likely to be highly efficacious in humans affected by AMD. SN - 1099-498X UR - https://www.unboundmedicine.com/medline/citation/12731088/Multiple_muscles_in_the_AMD_quail_can_be_"cross_corrected"_of_pathologic_glycogen_accumulation_after_intravenous_injection_of_an_[E1__polymerase_]_adenovirus_vector_encoding_human_acid_alpha_glucosidase_ L2 - https://doi.org/10.1002/jgm.355 DB - PRIME DP - Unbound Medicine ER -