Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease

被引：44

作者：

Ashe, Karen M. ^{[1
]}

Taylor, Kristin M. ^{[1
]}

Chu, Qiuming ^{[1
]}

Meyers, Elizabeth ^{[1
]}

Ellis, Allen ^{[1
]}

Jingozyan, Varvara ^{[1
]}

Klinger, Katherine ^{[1
]}

Finn, Patrick F. ^{[1
]}

Cooper, Christopher G. F. ^{[1
]}

Chuang, Wei-Lien ^{[1
]}

Marshall, John ^{[1
]}

McPherson, John M. ^{[1
]}

Mattaliano, Robert J. ^{[1
]}

Cheng, Seng H. ^{[1
]}

Scheule, Ronald K. ^{[1
]}

Moreland, Rodney J. ^{[1
]}

机构：

[1] Genzyme Corp, Framingham, MA 01701 USA

来源：

MOLECULAR GENETICS AND METABOLISM | 2010年 / 100卷 / 04期

关键词：

mTOR; Pompe disease; Glycogen storage disease; Glycogen synthase; Rapamycin; Enzyme replacement therapy; ACID ALPHA-GLUCOSIDASE; ENZYME REPLACEMENT THERAPY; HUMAN MUSCLE-CELLS; SKELETAL-MUSCLE; ALGLUCOSIDASE ALPHA; MAMMALIAN TARGET; INFANTILE; INSULIN; RAPAMYCIN; AUTOPHAGY;

D O I：

10.1016/j.ymgme.2010.05.001

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Pompe disease, also known as glycogen storage disease (GSD) type II, is caused by deficiency of lysosomal acid a-glucosidase (GAA). The resulting glycogen accumulation causes a spectrum of disease severity ranging from a rapidly progressive course that is typically fatal by 1-2 years of age to a more slowly progressive course that causes significant morbidity and early mortality in children and adults. Recombinant human GAA (rhGAA) improves clinical outcomes with variable results. Adjunct therapy that increases the effectiveness of rhGAA may benefit some Pompe patients. Co-administration of the mTORC1 inhibitor rapamycin with rhGAA in a GAA knockout mouse reduced muscle glycogen content more than rhGAA or rapamycin alone. These results suggest mTORC1 inhibition may benefit GSDs that involve glycogen accumulation in muscle. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：309 / 315

页数：7

共 34 条

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