Tags

Type your tag names separated by a space and hit enter

Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA.
J Gene Med 2005; 7(2):171-8JG

Abstract

BACKGROUND

Glycogen storage disease II (GSD-II) is an autosomal recessive lysosomal storage disease, due to acid-alpha-glucosidase (GAA) deficiency. The disease is characterized by massive glycogen accumulation in the cardiac and skeletal muscles. There is early onset (infantile, also known as Pompe disease) as well as late onset (juvenile and adult) forms of GSD-II. Few studies have been published to date that have explored the consequences of delivering a potential therapy to either late onset GSD-II subjects, and/or early onset patients with long-established muscle pathology. One recent report utilizing GAA-KO mice transgenically expressing human GAA (hGAA) suggested that long-established disease in both cardiac and skeletal muscle is likely to prove resistant to therapies. To investigate the potential for disease reversibility in old GSD-II mice, we studied their responsiveness to exogenous hGAA exposure via a gene therapy approach that we have previously shown to be efficacious in young GAA-KO mice.

METHODS

An [E1-, polymerase-] adenoviral vector encoding hGAA was intravenously injected into two groups of aged GAA-KO mice; GAA expression and tissue glycogen reduction were evaluated.

RESULTS

After vector injection, we found that extremely high amounts of hepatically secreted hGAA could be produced, and subsequently taken up by multiple muscle tissues in the old GAA-KO mice by 17 days post-injection (dpi). As a result, all muscle groups tested in the old GAA-KO mice showed significant glycogen reductions by 17 dpi, relative to that of age-matched, but mock-injected GAA-KO mice. For example, glycogen reduction in heart was 84%, in quadriceps 46%, and in diaphragm 73%. Our data also showed that the uptake and the subsequent intracellular processing of virally expressed hGAA were not impaired in older muscles.

CONCLUSIONS

Overall, the previously reported 'resistance' of old GAA-KO muscles to exogenous hGAA replacement approaches can be rapidly overcome after a single intravenous injection with a modified adenoviral vector expressing hGAA.

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 available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15515143

Citation

Xu, Fang, et al. "Glycogen Storage in Multiple Muscles of Old GSD-II Mice Can Be Rapidly Cleared After a Single Intravenous Injection With a Modified Adenoviral Vector Expressing HGAA." The Journal of Gene Medicine, vol. 7, no. 2, 2005, pp. 171-8.
Xu F, Ding E, Migone F, et al. Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA. J Gene Med. 2005;7(2):171-8.
Xu, F., Ding, E., Migone, F., Serra, D., Schneider, A., Chen, Y. T., & Amalfitano, A. (2005). Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA. The Journal of Gene Medicine, 7(2), pp. 171-8.
Xu F, et al. Glycogen Storage in Multiple Muscles of Old GSD-II Mice Can Be Rapidly Cleared After a Single Intravenous Injection With a Modified Adenoviral Vector Expressing HGAA. J Gene Med. 2005;7(2):171-8. PubMed PMID: 15515143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA. AU - Xu,Fang, AU - Ding,Enyu, AU - Migone,Felicia, AU - Serra,Delila, AU - Schneider,Ayn, AU - Chen,Yuan-Tsong, AU - Amalfitano,Andrea, PY - 2004/10/30/pubmed PY - 2005/6/18/medline PY - 2004/10/30/entrez SP - 171 EP - 8 JF - The journal of gene medicine JO - J Gene Med VL - 7 IS - 2 N2 - BACKGROUND: Glycogen storage disease II (GSD-II) is an autosomal recessive lysosomal storage disease, due to acid-alpha-glucosidase (GAA) deficiency. The disease is characterized by massive glycogen accumulation in the cardiac and skeletal muscles. There is early onset (infantile, also known as Pompe disease) as well as late onset (juvenile and adult) forms of GSD-II. Few studies have been published to date that have explored the consequences of delivering a potential therapy to either late onset GSD-II subjects, and/or early onset patients with long-established muscle pathology. One recent report utilizing GAA-KO mice transgenically expressing human GAA (hGAA) suggested that long-established disease in both cardiac and skeletal muscle is likely to prove resistant to therapies. To investigate the potential for disease reversibility in old GSD-II mice, we studied their responsiveness to exogenous hGAA exposure via a gene therapy approach that we have previously shown to be efficacious in young GAA-KO mice. METHODS: An [E1-, polymerase-] adenoviral vector encoding hGAA was intravenously injected into two groups of aged GAA-KO mice; GAA expression and tissue glycogen reduction were evaluated. RESULTS: After vector injection, we found that extremely high amounts of hepatically secreted hGAA could be produced, and subsequently taken up by multiple muscle tissues in the old GAA-KO mice by 17 days post-injection (dpi). As a result, all muscle groups tested in the old GAA-KO mice showed significant glycogen reductions by 17 dpi, relative to that of age-matched, but mock-injected GAA-KO mice. For example, glycogen reduction in heart was 84%, in quadriceps 46%, and in diaphragm 73%. Our data also showed that the uptake and the subsequent intracellular processing of virally expressed hGAA were not impaired in older muscles. CONCLUSIONS: Overall, the previously reported 'resistance' of old GAA-KO muscles to exogenous hGAA replacement approaches can be rapidly overcome after a single intravenous injection with a modified adenoviral vector expressing hGAA. SN - 1099-498X UR - https://www.unboundmedicine.com/medline/citation/15515143/Glycogen_storage_in_multiple_muscles_of_old_GSD_II_mice_can_be_rapidly_cleared_after_a_single_intravenous_injection_with_a_modified_adenoviral_vector_expressing_hGAA_ L2 - https://doi.org/10.1002/jgm.660 DB - PRIME DP - Unbound Medicine ER -