scholarly journals Moss-Derived Human Recombinant GAA Provides an Optimized Enzyme Uptake in Differentiated Human Muscle Cells of Pompe Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2642 ◽  
Author(s):  
Stefan Hintze ◽  
Sarah Limmer ◽  
Paulina Dabrowska-Schlepp ◽  
Birgit Berg ◽  
Nicola Krieghoff ◽  
...  

Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of lysosomal acid alpha-glucosidase (GAA). The result of the GAA deficiency is a ubiquitous lysosomal and non-lysosomal accumulation of glycogen. The most affected tissues are heart, skeletal muscle, liver, and the nervous system. Replacement therapy with the currently approved enzyme relies on M6P-mediated endocytosis. However, therapeutic outcomes still leave room for improvement, especially with regard to skeletal muscles. We tested the uptake, activity, and effect on glucose metabolism of a non-phosphorylated recombinant human GAA produced in moss (moss-GAA). Three variants of moss-GAA differing in glycosylation pattern have been analyzed: two with terminal mannose residues in a paucimannosidic (Man3) or high-mannose (Man 5) configuration and one with terminal N-acetylglucosamine residues (GnGn). Compared to alglucosidase alfa the moss-GAA GnGn variant showed increased uptake in differentiated myotubes. Moreover, incubation of immortalized muscle cells of Gaa−/− mice with moss-GAA GnGn led to similarly efficient clearance of accumulated glycogen as with alglucosidase alfa. These initial data suggest that M6P-residues might not always be necessary for the cellular uptake in enzyme replacement therapy (ERT) and indicate the potential of moss-GAA GnGn as novel alternative drug for targeting skeletal muscle in Pompe patients.

2018 ◽  
Vol 123 (2) ◽  
pp. 92-96 ◽  
Author(s):  
Ankit K. Desai ◽  
Crista K. Walters ◽  
Heidi L. Cope ◽  
Zoheb B. Kazi ◽  
Stephanie M. DeArmey ◽  
...  

2014 ◽  
Vol 9 (1) ◽  
pp. 75 ◽  
Author(s):  
Tim A Kanters ◽  
Iris Hoogenboom-Plug ◽  
Maureen PMH Rutten-Van Mölken ◽  
W Redekop ◽  
Ans T van der Ploeg ◽  
...  

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