BIOMAT Database Logo BIOMAT Database Logo

Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. 2001

A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

OBJECTIVE Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. METHODS The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. RESULTS The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. CONCLUSIONS This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006003 Glycogen
D006009 Glycogen Storage Disease Type II An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4) Acid Maltase Deficiency Disease,Generalized Glycogenosis,Glycogenosis 2,Lysosomal alpha-1,4-Glucosidase Deficiency Disease,Pompe Disease,Acid Alpha-Glucosidase Deficiency,Acid Maltase Deficiency,Adult Glycogen Storage Disease Type II,Alpha-1,4-Glucosidase Deficiency,Deficiency Disease, Acid Maltase,Deficiency Disease, Lysosomal alpha-1,4-Glucosidase,Deficiency of Alpha-Glucosidase,GAA Deficiency,GSD II,GSD2,Glycogen Storage Disease II,Glycogen Storage Disease Type 2,Glycogen Storage Disease Type II, Adult,Glycogen Storage Disease Type II, Infantile,Glycogen Storage Disease Type II, Juvenile,Glycogenosis Type II,Infantile Glycogen Storage Disease Type II,Juvenile Glycogen Storage Disease Type II,Pompe's Disease,Acid Alpha Glucosidase Deficiency,Acid Alpha-Glucosidase Deficiencies,Acid Maltase Deficiencies,Alpha 1,4 Glucosidase Deficiency,Alpha-1,4-Glucosidase Deficiencies,Alpha-Glucosidase Deficiencies,Alpha-Glucosidase Deficiencies, Acid,Alpha-Glucosidase Deficiency,Alpha-Glucosidase Deficiency, Acid,Deficiencies, Acid Alpha-Glucosidase,Deficiencies, Acid Maltase,Deficiencies, Alpha-1,4-Glucosidase,Deficiencies, GAA,Deficiency of Alpha Glucosidase,Deficiency, Acid Alpha-Glucosidase,Deficiency, Acid Maltase,Deficiency, Alpha-1,4-Glucosidase,Deficiency, GAA,Disease, Pompe,Disease, Pompe's,GAA Deficiencies,GSD2s,Generalized Glycogenoses,Glycogenoses, Generalized,Glycogenosis, Generalized,Lysosomal alpha 1,4 Glucosidase Deficiency Disease,Maltase Deficiencies, Acid,Pompes Disease,Type II, Glycogenosis,Type IIs, Glycogenosis
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts

Related Publications

A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial.
January 2005, Neuromuscular disorders : NMD,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.
January 2007, Neurology,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Juvenile-onset glycogen storage disease type II with novel mutations in acid alpha-glucosidase gene.
February 2003, Neurology,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
[Clinical features and acid alpha-glucosidase gene mutation in 7 Chinese patients with glycogen storage disease type II].
July 2013, Zhonghua yi xue za zhi,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II.
November 1999, Human molecular genetics,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
A novel acid alpha-glucosidase mutation identified in a Pakistani family with glycogen storage disease type II.
August 1997, Journal of inherited metabolic disease,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Canine glycogen storage disease type II. A biochemical study of an acid alpha-glucosidase-deficient Lapland dog.
March 1982, Biochimica et biophysica acta,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Pompe disease (glycogen storage disease type II): clinical features and enzyme replacement therapy.
June 2006, Acta neurologica Belgica,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid alpha-glucosidase deficiency).
November 1984, American journal of medical genetics,
A Amalfitano, and A R Bengur, and R P Morse, and J M Majure, and L E Case, and D L Veerling, and J Mackey, and P Kishnani, and W Smith, and A McVie-Wylie, and J A Sullivan, and G E Hoganson, and J A Phillips, and G B Schaefer, and J Charrow, and R E Ware, and E H Bossen, and Y T Chen
Identification of eight novel mutations of the acid alpha-glucosidase gene causing the infantile or juvenile form of glycogen storage disease type II.
June 2008, Journal of neurology,
Copied contents to your clipboard!