Evaluation of Systemic Follistatin as an Adjuvant to Stimulate Muscle Repair and Improve Motor Function in Pompe Mice
| Autor: | Joseph W. Foley, Robin J. Ziegler, Scott D. Bercury, Patrick Finn, Seng H. Cheng, Ronald K. Scheule |
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| Rok vydání: | 2010 |
| Předmět: |
Follistatin
medicine.medical_specialty Genetic Vectors Myostatin Body Mass Index Muscle hypertrophy Mice Grip strength chemistry.chemical_compound Internal medicine Glycogen storage disease type II Drug Discovery medicine Genetics Animals Humans Muscular dystrophy Muscle Skeletal Molecular Biology Pharmacology biology Glycogen Glycogen Storage Disease Type II Skeletal muscle alpha-Glucosidases Dependovirus medicine.disease Mice Inbred C57BL Disease Models Animal Endocrinology medicine.anatomical_structure chemistry biology.protein Molecular Medicine Original Article |
| Zdroj: | Molecular Therapy. 18(9):1584-1591 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2010.110 |
| Popis: | Due to the lack of acid alpha-glucosidase (GAA) activity, Pompe mice develop glycogen storage pathology and progressive skeletal muscle dysfunction with age. Applying either gene or enzyme therapy to reconstitute GAA levels in older, symptomatic Pompe mice effectively reduces glycogen storage in skeletal muscle but provides only modest improvements in motor function. As strategies to stimulate muscle hypertrophy, such as by myostatin inhibition, have been shown to improve muscle pathology and strength in mouse models of muscular dystrophy, we sought to determine whether these benefits might be similarly realized in Pompe mice. Administration of a recombinant adeno-associated virus serotype 8 vector encoding follistatin, an inhibitor of myostatin, increased muscle mass and strength but only in Pompe mice that were treated before 10 months of age. Younger Pompe mice showed significant muscle fiber hypertrophy in response to treatment with follistatin, but maximal gains in muscle strength were achieved only when concomitant GAA administration reduced glycogen storage in the affected muscles. Despite increased grip strength, follistatin treatment failed to improve rotarod performance. These findings highlight the importance of treating Pompe skeletal muscle before pathology becomes irreversible, and suggest that adjunctive therapies may not be effective without first clearing skeletal muscle glycogen storage with GAA. |
| Databáze: | OpenAIRE |
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