1. Alglucosidase alfa (Approved drug) DB01272
Chemical Formula : C4435H6739N1175O1279S32
Protein weight :
Category : Enzyme Replacement Agents
Use : For the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.
Target : Cation-dependent mannose-6-phosphate receptor,Glycogen
Half life : 2.3 hr with 17% coefficient of variation.
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.

2. 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. Mode 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.

3. Volume of distribution : 96 ± 16 mL/kg [20 mg/kg dose] 119 ± 28 mL/kg [40 mg/kg dose] Route of elimination : Via kidney and liver Clearance : 25+/- 4 mL/hr/kg [4-hour IV infusion of 20 mg/kg] Brands : Lumizyme and Genzyme’s Myozyme Lumizyme 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). Alglucosidase alfa is intended for intravenous infusion. It is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with 10.3 mL Sterile Water for Injection, USP. 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. Recommended dose : The recommended dosage of alglucosidase alfa is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion. Dosage form : For injection: 50 mg of alglucosidase alfa is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder in a single-use vial for reconstitution. After reconstitution, the resultant solution concentration is 5 mg/mL.

4. Myozyme
Myozyme (alglucosidase alfa) contains an enzyme that naturally occurs in the body in healthy people. Some people lack this enzyme because of a genetic disorder. Alglucosidase alfa helps replace this missing enzyme in such people.
Myozyme is used to treat a glycogen storage disorder called Pompe disease, (also called GAA deficiency) in adults and children who are at least 8 years old.
Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease
Administration : Myozyme is injected into a vein through an IV. A healthcare provider will give you this injection. Myozyme must be given slowly, and the IV infusion can take up to 4 hours to complete. This medicine is usually given once every 2 weeks. Before each injection, tell your doctor if you have recently been sick with a cold, flu, or other illness. If you need surgery, tell the surgeon ahead of time that you are using Myozyme. Myozyme can have long lasting effects on your body. Your blood will need to be tested every 3 months for 2 years and then once every year after that.

5. Usual Adult Dose of Myozyme for Pompe disease: 20 mg/kg via IV infusion every 2 weeks Comments: -Total volume of infusion is determined by patient's body weight and should be infused over about 4 hours. Usual Pediatric Dose for Pompe disease: 20 mg/kg via IV infusion every 2 weeks Comments: -Total volume of infusion is determined by body weight and should be infused over about 4 hours. Drug interactions : Other drugs may interact with alglucosidase alfa, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

6. General reference : 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 Jan 9;68(2): Epub 2006 Dec 6. "Pubmed":