Dose Finding Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
Summary
This is a single-center, open-label, multiple-dose study of the efficacy and long-term safety of Lamazym for the treatment of patients with alpha-mannosidosis.
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Alpha Mannosidosis
Intervention
Lamazym
Location
Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
Copenhagen
Denmark
2100
Status
Active, not recruiting
Source
Zymenex A/S
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01285700
- Information obtained from ClinicalTrials.gov on October 23, 2012
Medical and Biotech [MESH] Definitions
Alpha-mannosidase
An enzyme that catalyzes the HYDROLYSIS of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. The enzyme plays a role in the processing of newly formed N-glycans and in degradation of mature GLYCOPROTEINS. There are multiple isoforms of alpha-mannosidase, each having its own specific cellular location and pH optimum. Defects in the lysosomal form of the enzyme results in a buildup of mannoside intermediate metabolites and the disease ALPHA-MANNOSIDOSIS.
Alpha-mannosidosis
An inborn error of metabolism marked by a defect in the lysosomal isoform of ALPHA-MANNOSIDASE activity that results in lysosomal accumulation of mannose-rich intermediate metabolites. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder.
Prostaglandins F
(9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.
Glycogen Debranching Enzyme System
1,4-alpha-D-Glucan-1,4-alpha-D-glucan 4-alpha-D-glucosyltransferase/dextrin 6 alpha-D-glucanohydrolase. An enzyme system having both 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities. As a transferase it transfers a segment of a 1,4-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or another 1,4-alpha-D-glucan. As a glucosidase it catalyzes the endohydrolysis of 1,6-alpha-D-glucoside linkages at points of branching in chains of 1,4-linked alpha-D-glucose residues. Amylo-1,6-glucosidase activity is deficient in glycogen storage disease type III.
Alpha-glucosidases
Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.
Clinical Trials
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PubMed Articles
In Alpha-mannosidosis (MIM 248500) the patients accumulate mainly unbranched oligosaccharide chains in the lysosomes in all body tissues, including the brain. With ensuing therapeutic modalities in ma...
Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients.
Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi instituti...
β-Mannosidosis results from a functional deficiency of the lysosomal enzyme, β-mannosidase. While being a well recognised, naturally occurring disease in both goats and cattle, it is an extremely ra...
Deficiency in human lysosomal α-mannosidase (MAN2B1) results in α-mannosidosis, a lysosomal storage disorder; patients present a wide range of neurological, immunological, and skeletal symptoms caus...
α-Mannosidosis, OMIM #248500, is an autosomal recessive lysosomal storage disease caused by acidic α-mannosidase deficiency. Treatment options include bone marrow transplantation (BMT) and, possibly...
