Alglucosidase alfa

Identification

Name
Alglucosidase alfa
Accession Number
DB01272
Description

Aglucosidase alfa consists of the human enzyme acid alpha-glucosidase (GAA) which is essential for the degradation of glygogen to glucose in lysosomes. It is encoded by the most predominant of nine observed haplotypes of this gene. Aglucosidase alfa is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of a-1,4- and a-1,6- glycosidic linkages of lysosomal glycogen. Structurally, Alglucosidase alfa is a glycoprotein with a calculated mass of 98,008 daltons for the 883 residue mature polypeptide chain, and a total mass of approximately 109,000 daltons, including carbohydrates. It is used for the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Structure
Db01272
Protein Chemical Formula
C4435H6739N1175O1279S32
Protein Average Weight
105270.802 Da
Sequences
>Alglucosidase alfa
AHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGAQMGQPWCFF
PPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLHFTIKDPANR
RYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLFFADQFLQLS
TSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLALEDGGSAHG
VFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGYPFMPPYWGL
GFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDGFRDFPAMVQ
ELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKVWPGSTAFPD
FTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELENPPYVPGVVG
GTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISRSTFAGHGRY
AGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVRWTQLGAFYP
FMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAGETVARPLFL
EFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPVEALGSLPPP
PAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQPMALAVALTK
GGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQLQKVTVLGV
ATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
Download FASTA Format
Synonyms
  • Acid maltase
  • Acid-alpha glucosidase
  • Aglucosidase alfa
  • Aglucosidase alpha
  • Alglucosidasa alfa
  • alpha-1,4-glucosidase
  • Alpha-glucosidase
  • Lysosomal Alpha-Glucosidase

Pharmacology

Indication

For the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Pompe disease (glycogen storage disease type II, GSD II, glycogenosis type II, acid maltase deficiency) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. In the infantile-onset form, Pompe disease results in intralysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, and hepatic tissues, leading to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function. In the juvenile- and adult-onset forms, intralysosomal accumulation of glycogen is limited primarily to skeletal muscle, resulting in progressive muscle weakness. Death in all forms is usually related to respiratory failure. Alglucosidase alfa provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.

Mechanism of action

Alglucosidase alfa is designed to act as an exogenous source of GAA, acting to correct GAA deficiency that is the hallmark of Pompe disease. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen. Specifically, it hydrolyses alpha-1,4-glucose bonds.

TargetActionsOrganism
ACation-dependent mannose-6-phosphate receptor
binder
Humans
AGlycogen
cleavage
Humans
Absorption
Not Available
Volume of distribution
  • 96 ± 16 mL/kg [20 mg/kg dose]
  • 119 ± 28 mL/kg [40 mg/kg dose]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Via kidney and liver

Half-life

2.3 ± 0.4 hours.

Clearance
  • 25+/- 4 mL/hr/kg [4-hour IV infusion of 20 mg/kg]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

There have been no reports of overdose with alglucosidase alfa.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
No interactions found.
Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LumizymeInjection, powder, for solution5 mg/1mLIntravenousGenzyme Corporation2010-05-24Not applicableUS flag
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEU flag
MyozymePowder, for solution50 mgIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2006-12-06Not applicableCanada flag
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEU flag
MyozymeInjection, powder, lyophilized, for solution5 mg/1mLIntravenousGenzyme Corporation2010-06-192015-11-30US flag
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
A16AB07 — Alglucosidase alfa
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
DTI67O9503
CAS number
420784-05-0

References

General References
  1. Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, Leslie N, Levine J, Spencer C, McDonald M, Li J, Dumontier J, Halberthal M, Chien YH, Hopkin R, Vijayaraghavan S, Gruskin D, Bartholomew D, van der Ploeg A, Clancy JP, Parini R, Morin G, Beck M, De la Gastine GS, Jokic M, Thurberg B, Richards S, Bali D, Davison M, Worden MA, Chen YT, Wraith JE: Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007 Jan 9;68(2):99-109. Epub 2006 Dec 6. [PubMed:17151339]
KEGG Drug
D03207
PubChem Substance
46504595
RxNav
629565
ChEMBL
CHEMBL1201824
Therapeutic Targets Database
DAP001289
PharmGKB
PA164754753
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alglucosidase_alfa
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (1.11 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II (GSD-II) / Pompe's Disease1
4Active Not RecruitingTreatmentGlycogen Storage Disease Type II1
4CompletedTreatmentAcid Maltase Deficiency (AMD) / Glycogen Storage Disease Type II (GSD-II) / Glycogenesis Type II / Pompe Disease (Late-Onset)1
4CompletedTreatmentDiabetes / Type 2 Diabetes Mellitus1
4CompletedTreatmentGlycogen Storage Disease Type II (GSD II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe Disease (Late-Onset)1
4CompletedTreatmentGlycogen Storage Disease Type II (GSD-II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe's Disease1
4CompletedTreatmentGlycogen Storage Disease Type II / Pompe's Disease1
4CompletedTreatmentType 2 Diabetes Mellitus1
4RecruitingOtherGlycogen Storage Disease Type II (GSD II) / Pompe Disease (Late-Onset)1
4TerminatedTreatmentAcid Maltase Deficiency (AMD) / Glycogen Storage Disease Type II (GSD II) / Glycogenosis 2 / Pompe Disease (Infantile-Onset)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genzyme Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous5 mg/1mL
Injection, powder, for solution
Injection, powder, for solutionIntravenous50 mg
Injection, powder, lyophilized, for solutionIntravenous5 mg/1mL
Injection, solution, concentrateIntravenous50 mg
Powder, for solutionIntravenous50 mg
Prices
Unit descriptionCostUnit
Myozyme 50 mg vial720.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2416492No2008-04-292021-07-10Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Transmembrane signaling receptor activity
Specific Function
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate r...
Gene Name
M6PR
Uniprot ID
P20645
Uniprot Name
Cation-dependent mannose-6-phosphate receptor
Molecular Weight
30993.06 Da
References
  1. Chavez CA, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Dahms NM: Domain 5 of the cation-independent mannose 6-phosphate receptor preferentially binds phosphodiesters (mannose 6-phosphate N-acetylglucosamine ester). Biochemistry. 2007 Nov 6;46(44):12604-17. Epub 2007 Oct 10. [PubMed:17927214]
2. Glycogen
Kind
Group
Organism
Humans
Pharmacological action
Yes
Actions
Cleavage
References
  1. Hu D, Kamiya Y, Totani K, Kamiya D, Kawasaki N, Yamaguchi D, Matsuo I, Matsumoto N, Ito Y, Kato K, Yamamoto K: Sugar-binding activity of the MRH domain in the ER alpha-glucosidase II beta subunit is important for efficient glucose trimming. Glycobiology. 2009 Oct;19(10):1127-35. doi: 10.1093/glycob/cwp104. Epub 2009 Jul 22. [PubMed:19625484]
  2. Christiansen C, Hachem MA, Glaring MA, Vikso-Nielsen A, Sigurskjold BW, Svensson B, Blennow A: A CBM20 low-affinity starch-binding domain from glucan, water dikinase. FEBS Lett. 2009 Apr 2;583(7):1159-63. doi: 10.1016/j.febslet.2009.02.045. Epub 2009 Mar 9. [PubMed:19275898]

Drug created on May 16, 2007 14:19 / Updated on October 27, 2020 11:13

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