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| Primary information |
|---|
| ID | 10521 |
| Therapeutic ID | Th1101 |
| Protein Name | Galsulfase |
| Sequence | >Th1101_Galsulfase
SGAGASRPPHLVFLLADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRSQLLTGRYQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRKECLPTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVATGYKNMYSTNIFTKRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPYDFIQDKNRHHYAGMVSLMDEAVGNVTAALKSSGLWNNTVFIFSTDNGGQTLAGGNNWPLRGRKWSLWEGGVRGVGFVASPLLKQKGVKNRELIHISDWLPTLVKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNIDPNFVDSSPCPRNSMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQYNVSEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSVPVYFPAQDPRCDPKATGVWGPWM
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| Molecular Weight | 56012.6 |
| Chemical Formula | C2534H3851N691O719S16 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week.. |
| Description | A recombinant variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase. It is a glycoprotein with a molecular weight of approximately 56 kD and comprises 495 amino acids. It contains 6 N-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate manose7 oligosaccharide for specific cellular recognition. It requires Ca-formylglycine for its catalytic activity. This residue is a post-translational modification of Cys53 and conserved in all members of the sulfatase enzyme family. |
| Indication/Disease | For the treatment of adults and children with Mucopolysaccharidosis VI. |
| Pharmacodynamics | Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. Galsulfase is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors. |
| Mechanism of Action | Galsulfase supplies recombinant-engineered galsulfase, a normal variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase. It is a lysosomal hydrolase that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of GAG chondroitin 4-sulfate and dermatan sulfate. Increased catabolism of GAG in turn reduces systemic dermatan sulfate accumulation, thereby reducing the primary symptoms of MPS VI. |
| Toxicity | There is no experience with overdose of galsulfase. |
| Metabolism | NA |
| Absorption | NA |
| Week 1: 56-323 mL/kg and 59-2799 mL/kg by week 24 |
| Clearance | NA |
| Categories | Enzyme Replacement Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Dermatan sulfate,Perilipin-3 |
| Brand Name | Naglazyme |
| Company | BioMarin |
| Brand Description | BioMarin |
| Prescribed For | NAGLAZYME (galsulfase) is indicated for patients with Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity. |
| Chemical Name | NA |
| Formulation | NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only. |
| Physical Appearance | Sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The recommended dosage regimen of NAGLAZYME is 1 mg per kg of body weight administered once weekly as an Intravenous infusion. Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion. |
| Contraindication | NA |
| Side Effects | Serious adverse reactions experienced in this trial include apnea, pyrexia, and respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions requiring interventions were infusion reactions. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |