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| Primary information |
|---|
| ID | 10503 |
| Therapeutic ID | Th1097 |
| Protein Name | Alglucosidase alfa |
| Sequence | >Th1097_Alglucosidase_alfa
AHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGAQMGQPWCFFPPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLHFTIKDPANRRYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLFFADQFLQLSTSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLALEDGGSAHGVFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGYPFMPPYWGLGFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDGFRDFPAMVQELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKVWPGSTAFPDFTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELENPPYVPGVVGGTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISRSTFAGHGRYAGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVRWTQLGAFYPFMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAGETVARPLFLEFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPVEALGSLPPPPAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQPMALAVALTKGGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQLQKVTVLGVATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
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| Molecular Weight | 105270.8 |
| Chemical Formula | C4435H6739N1175O1279S32 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 2.3 ± 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 | NA |
| Absorption | NA |
| 96 ± 16 mL/kg [20 mg/kg dose] 119 ± 28 mL/kg [40 mg/kg dose] |
| Clearance | 25+/- 4 mL/hr/kg [4-hour IV infusion of 20 mg/kg] |
| Categories | Alimentary Tract and Metabolism,alpha-Glucosidases,Enzymes,Enzymes and Coenzymes,Glucosidases,Glycogen Storage Disease Type II,Glycoside Hydrolases,Hydrolases,Hydrolytic Lysosomal Glycogen-specific Enzyme |
| Patents Number | CA2416492 |
| Date of Issue | 29-Apr-2008 |
| Date of Expiry | 10-Jul-2021 |
| Drug Interaction | NA |
| Target | Cation-dependent mannose-6-phosphate receptor,Glycogen |
| Brand Name | LUMIZYME |
| Company | Genzyme |
| Brand Description | Genzyme |
| Prescribed For | LUMIZYME (alglucosidase alfa) [see DESCRIPTION] is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase (GAA) deficiency). |
| Chemical Name | NA |
| 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. |
| Physical Appearance | 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 | NA |
| Side Effects | In clinical trials, the most common adverse reactions ( ≥ 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 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |