Alglucosidase alfa
Based on 1 Customer Validation
Alglucosidase alfa (rhGAA) is a recombinant human acid α-glucosidase. Alglucosidase alfa is taken up by cells via the cation-independent mannose-6-phosphate receptor (CI-MPR) pathway and transported to lysosomes, where GAA degrades glycogen in the acidic lysosomal environment. Alglucosidase alfa is applicable to research related to lysosomal glycogen metabolism and glycogen storage diseases.
For research use only. We do not sell to patients.
- Purity : 98%
- CAS No.: 420784-05-0
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vivo
Neither alglucosidase alfa (120 µg; intracranial injection; single dose; analyzed 7 days post-injection) nor alglucosidase alfa (13.2-17.2 µg/day; intracranial injection; continuous infusion; 14-30 days) reduces the number of Lafora bodies, brain glycogen levels, or improves behavioral outcomes in Epm2a-/- knockout mice with Lafora disease[2].
Alglucosidase alfa (40 mg/kg; i.v.; once weekly; 4 weeks) reduces hepatic glycogen accumulation by 21% in GSD IV mice, but does not significantly decrease glycogen in skeletal muscle; a dose of 20 mg/kg does not produce a significant reduction in glycogen accumulation in the tested tissues[4].
Long-term administration of alglucosidase alfa (20 mg/kg; intravenous injection; once every two weeks; 2 doses total) fails to improve muscle function, myofiber size, or dysferlin localization in Gaa-KO mice[1].
Following administration of alglucosidase alfa (20 mg/kg; i.v.; once every 2 weeks, for a total of 4 doses), extensive Lamp1/LC3-positive autophagic accumulation remains in the muscle fibers of Gaa-KO mice, with over 95% of the examined muscle fibers still containing such autophagic accumulation[1].
Alglucosidase alfa (20 mg/kg; i.v.; weekly; 12 weeks) induces anti-rhGAA-specific IgG responses in E4-8GAAKO Pompe mice; upon re-exposure after a 4-week withdrawal, the antibody response is further elevated in the rhGAA-alone group, whereas the group receiving combined treatment with low-dose Methotrexate (HY-14519) maintains low antibody levels[3].
Alglucosidase alfa (20 or 40 mg/kg; i.v.; once weekly; 4 weeks) dose-dependently increases GAA activity in multiple tissues of Gbe1ys/ys GSD IV mice; GAA activity in the liver increases by 29-fold and 48-fold in the 20 mg/kg and 40 mg/kg groups, respectively, while that in the heart increases by 1.7-fold and 2.8-fold, respectively, with only a slight increase observed in the quadriceps femoris[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:129SVE (male, 14-16 weeks old, Gaa-knockout)[1]
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Dosage:20 mg/kg
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Administration:i.v.; biweekly; 2 doses
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Result:Reduced glycogen storage by 27.5% in quadriceps, 21.2% in gastrocnemius, 14.6% in triceps, and 45.2% in heart.
Showed limited reduction in lysosomal Lamp1 signal in quadriceps, heart, and diaphragm, with greater effect in type I muscle fibers.
Did not reduce autophagic buildup (over 95% of muscle fibers retained autophagic accumulation).
Had no effect on phosphorylation levels of glycogen synthase kinase 3β (p-GSK S9) or glycogen synthase (p-GS S641).
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Animal Model:129SVE (male, 16 weeks old, Gaa-knockout)[1]
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Dosage:20 mg/kg
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Administration:i.v.; biweekly; 4 doses
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Result:Did not improve muscle fiber size (minimum Feret’s diameter of quadriceps fibers was 32 μm, similar to vehicle-treated mice).
Did not reduce intracellular accumulation of dysferlin in quadriceps or triceps.
Did not improve grip strength or wire-hang test performance over 5 months of treatment.
Left prominent areas of autophagic debris visible in muscle fibers via second harmonic generation/2-photon excited fluorescence imaging.
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Animal Model:129SVE (male, 14 weeks old, Gaa-knockout)[1]
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Dosage:20 mg/kg
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Administration:i.v.; biweekly; 12 doses
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Result:Resulted in only a very small increase in quadriceps muscle fiber minimum Feret’s diameter compared with vehicle-treated mice.
Did not reduce abnormal intracellular dysferlin accumulation in quadriceps and triceps.
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Animal Model:Epm2aR240X knock-in (12-month-old; Lafora disease model)[2]
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Dosage:120 µg; 240 µg; 480 µg
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Administration:i.c.v.; single injection; 7 days post-injection analysis
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Result:Did not reduce the number of Lafora bodies in the hippocampal CA1 region following single i.c.v. injections of 120 µg, 240 µg, or 480 µg.
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Animal Model:C57BL/6J (8-12 weeks old); B6.129P2-IL10tm1Cgn/J (IL-10 knockout, 8-12 weeks old)[3]
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Dosage:20 mg/kg
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Administration:i.v.; weekly; 8 weeks
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Result:Reduced anti-alglucosidase alfa-specific IgG titers by 80% as measured by area under the curve in wild-type mice.
Did not reduce anti-alglucosidase alfa-specific titers in IL-10 knockout mice compared with alglucosidase alfa alone.
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Animal Model:C57BL/6J (8-12 weeks old)[3]
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Dosage:20 mg/kg
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Administration:i.v.; weekly
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Result:Did not interfere with methotrexate-mediated reduction of anti-alglucosidase alfa-specific IgG titers when active TGF-β was inhibited.
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Animal Model:E4-8GAA knockout (8-12 weeks old)[3]
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Dosage:20 mg/kg
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Administration:i.v.; weekly; 12 weeks; plus rechallenge dose
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Result:Reduced anti-alglucosidase alfa-specific IgG titers by 78% and 71%, respectively, as measured by area under the curve, with single-cycle and three-cycle methotrexate coadministration compared with alglucosidase alfa alone.
Did not increase anti-alglucosidase alfa IgG responses upon rechallenge in methotrexate-treated mice, unlike alglucosidase alfa-only treated mice.
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Animal Model:GSD IV (Gbe1ys/ys) (male, 10 weeks old at treatment initiation, spontaneous genetic mutation in Gbe1 gene)[4]
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Dosage:20 mg/kg; 40 mg/kg
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Administration:i.v.; weekly; 4 weeks
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Result:Dose-dependently increased tissue GAA activity.
40 mg/kg reduced hepatic glycogen by 21% and decreased liver/body weight ratio and plasma ALT.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Conjugated
Unconjugated
Reconsititution
The product can be reconstituted/diluted with sterile PBS or saline.
Chemical Information
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CAS No. 420784-05-0
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Appearance Solid
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Color White to off-white
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SMILES
[Alglucosidase alfa]
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Synonyms
rhGAA
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
Purity & Documentation
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Data Sheet (285 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
References
[3]. Joly MS, et al. Transient low-dose methotrexate generates B regulatory cells that mediate antigen-specific tolerance to alglucosidase alfa. Journal of immunology (Baltimore, Md. : 1950). 2014 Oct 15;193(8):3947-58. [Content Brief]
[4]. Yi H, et al. Alglucosidase alfa treatment alleviates liver disease in a mouse model of glycogen storage disease type IV. Molecular genetics and metabolism reports. 2016 Dec;9:31-33. [Content Brief]
[5]. Dornelles AD, et al. Efficacy and safety of enzyme replacement therapy with alglucosidase alfa for the treatment of patients with infantile-onset Pompe disease: a systematic review and metanalysis. Frontiers in pediatrics. 2024;12:1310317. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Alglucosidase alfa Related Classifications
HY-108828 Related Classifications
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