Highly potent acid alpha-glucosidase with enhanced carbohydrates
Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.
1. A method for modulating lysosomal proliferation or autophagy in a cell comprising administering to a subject a composition comprising recombinant human acid alpha-glucosidase (rhGAA) produced from Chinese hamster ovary (CHO) cells, wherein 40%-60% of the N-glycans on the rhGAA are complex type N-glycans and the rhGAA comprises 3.0-5.0 mol mannose-6-phosphate (M6P) residues per mol rhGAA.
2. The method of claim 1 , wherein the rhGAA comprises 3.0 to 4.0 mol M6P per mol rhGAA.
3. The method of claim 1 , wherein the rhGAA comprises 4.0 to 5.0 mol M6P per mol rhGAA.
4. The method of claim 1 , wherein about 45%-55% of the N-glycans on the rhGAA are complex type N-glycans.
5. The method of claim 1 , wherein 50% of the N-glycans on the rhGAA are complex type N-glycans.
6. The method of claim 1 , wherein the rhGAA comprises at least one bis-phosphorylated N-glycan per rhGAA.
7. The method of claim 1 , wherein the rhGAA further comprises
(a) 2.0 to 8.0 mol sialic acid per mol rhGAA; or
(b) at least 4 mol sialic acid per mol rhGAA.
8. The method of claim 1 , wherein the method further comprises administering a pharmacological chaperone, and wherein said composition and said pharmacological chaperone are either administered as a single pharmaceutical composition or administered separately.
9. The method of claim 8 , wherein the pharmacological chaperone is N-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the rhGAA is conjugated to a targeting moiety.
11. The method of claim 1 , wherein the method modulates lysosomal proliferation.
12. The method of claim 1 , wherein the method modulates autophagy.