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Primary information
ThPP ID	Th1097
Therapeutic Peptide/Protein Name	Alglucosidase alfa
Sequence	AHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQG view full sequnce in fasta
Functional Classification	Ic
Molecular Weight	105270.802
Chemical Formula	C4435H6739N1175O1279S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	2.3 Â± 0.4 hours.
Description	Recombinant (CHO cell derived) form of the human lysosomal enzyme, acid alpha-glucosidase (GAA), which is essential for the degradation of glygogen to glucose. It hydrolyses the alfa-1,4- and alfa-1,6- glycosidic linkages of lysosomal glycogen. The mature polypeptide is 883 residue long with a mass of 98,008 daltons and a total mass of approximately 109,000 daltons of the full-length glycosylated protein
Indication/Disease	For the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.
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.
Toxicity	There have been no reports of overdose with alglucosidase alfa.
Metabolism	N.A.
Absorption	N.A.
Volume of Distribution	96 Â± 16 mL/kg [20 mg/kg dose] 119 Â± 28 mL/kg [40 mg/kg dose]
Clearance	25Â±4 mL/hr/kg [4-hour IV infusion of 20 mg/kg]
Categories	Enzyme Replacement Agents
Patents Number	CA2416492
Date of Issue	30/04/12
Date of Expiry	11/07/25
Drug Interaction	N.A.
Target	Cation-dependent mannose-6-phosphate receptor,Glycogen
Information of corresponding available drug in the market
Brand Name	LUMIZYME
Company	Genzyme
Brand Discription	Alglucosidase alfa is a hydrolytic lysosomal glycogen-specific enzyme encoded by the predominant of nine observed haplotypes of the human acid a-glucosidase (GAA) gene. Alglucosidase 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. Alglucosidase alfa is a glycoprotein with a calculated mass of 99,377 daltons for the polypeptide chain, and a total mass of approximately 109,000 daltons, including carbohydrates. Alglucosidase alfa has a specific activity of 3.6 to 5.4 units/mg (one unit is defined as that amount of activity that results in the hydrolysis of 1 micromole of synthetic substrate per minute under specified assay conditions).
Prescribed for	LUMIZYME (alglucosidase alfa) [see DESCRIPTION] is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid Î±-glucosidase (GAA) deficiency).
Chemical Name	N.A.
Formulation	Each 50 mg vial contains 52.5 mg alglucosidase alfa, 210 mg mannitol, 0.5 mg polysorbate 80, 9.9 mg sodium phosphate dibasic heptahydrate, 31.2 mg sodium phosphate monobasic monohydrate. Following reconstitution as directed, each vial contains 10.5 mL reconstituted solution and a total extractable volume of 10 mL at 5 mg/mL alglucosidase alfa. Alglucosidase alfa does not contain preservatives; each vial is for single use only.
Physcial Appearnce	Sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with 10.3 Ml Sterile Water for Injection, USP
Route of Administration	Intravenous infusion
Recommended Dosage	The recommended dosage of alglucosidase alfa is 20 mg/kg body weight administered every 2 weeks as an Intravenous infusion.
Contraindication	N.A.
Side Effects	In clinical trials, the most common adverse reactions ( â‰¥ 5%) following alglucosidase alfa treatment were hypersensitivity reactions, and included anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.
Useful Link	http://www.rxlist.com/lumizyme-drug/side-effects-interactions.htm https://en.wikipedia.org/wiki/Alglucosidase_alfa http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm407563.htm
PubMed ID	25617983, 25345093, 25323875, 25260508
3-D Structure	N.A.