scholarly journals The molecular basis for Pompe disease revealed by the structure of human acid α-glucosidase

2017 ◽  
Author(s):  
Derrick Deming ◽  
Karen Lee ◽  
Tracey McSherry ◽  
Ronnie R. Wei ◽  
Tim Edmunds ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Molecular Basis ◽  
Glycogen Storage ◽  
Type Ii ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Human Acid ◽  
Glycogen Storage Disorder ◽  
Cellular Dysfunction ◽  
Disorder Type

AbstractPompe disease results from a defect in human acid α-glucosidase (GAA), a lysosomal enzyme that cleaves terminal α1-4 and α1-6 glucose from glycogen. In Pompe disease (also known as Glycogen Storage Disorder type II), the accumulation of undegraded glycogen in lysosomes leads to cellular dysfunction, primarily in muscle and heart tissues. Pompe disease is an active candidate of clinical research, with pharmacological chaperone therapy tested and enzyme replacement therapy approved. Despite production of large amounts of recombinant GAA annually, the structure of GAA has not been reported until now. Here, we describe the first structure of GAA, at 1.7Å resolution. Three structures of GAA complexes reveal the molecular basis for the hundreds of mutations that lead to Pompe disease and for pharmacological chaperoning in the protein. The GAA structure reveals a surprising second sugar-binding site 34Å from the active site, suggesting a possible mechanism for processing of large glycogen substrates. Overall, the structure will assist in the design of next-generation treatments for Pompe disease.

Correction of Glycogen Storage Disease Type II by Enzyme Replacement with a Recombinant Human Acid Maltase Produced by Over-Expression in a CHO-DHFRneg Cell Line

2000 ◽  
Vol 276 (3) ◽  
pp. 917-923 ◽  
Author(s):  
Frank Martiniuk ◽  
Agnes Chen ◽  
Vincent Donnabella ◽  
Eleni Arvanitopoulos ◽  
Alfred E. Slonim ◽  
...  
Keyword(s):  
Cell Line ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Ii ◽  
Over Expression ◽  
Enzyme Replacement ◽  
Acid Maltase ◽  
Human Acid

scholarly journals A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease

2021 ◽  
Vol 10 (21) ◽  
pp. 4828
Author(s):  
Alícia Dorneles Dornelles ◽  
Ana Paula Pedroso Junges ◽  
Tiago Veiga Pereira ◽  
Bárbara Corrêa Krug ◽  
Candice Beatriz Treter Gonçalves ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Late Onset ◽  
Meta Analysis ◽  
Glycogen Storage ◽  
Enzyme Replacement ◽  
Sf 36 ◽  
Glycogen Storage Disorder

Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change −2.64 h (95% CI −5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.

Providing the conduit for treatment: The impact of vascular access and vein preservation in a 5-year-old child with prenatally diagnosed CRIM-negative Infantile Pompe disease

2021 ◽  
pp. 112972982199948
Author(s):  
Matthew Ostroff ◽  
Punita Gupta ◽  
Daniel Garcia
Keyword(s):  
Vascular Access ◽  
Pompe Disease ◽  
Disease Patient ◽  
Tolerance Induction ◽  
Glycogen Storage ◽  
Glycogen Accumulation ◽  
Enzyme Replacement ◽  
Infantile Pompe Disease ◽  
Glycogen Storage Disorder ◽  
The Impact

Pompe disease is an autosomal recessive glycogen storage disorder resulting in progressive glycogen accumulation expressed in infancy with cardiomyopathy and skeletal myopathy. Without treatment by enzyme replacement therapy (ERT), life expectancy is less than 2 years. The cross-reactive immunologic material (CRIM) positive or negative status is the basis for the response to ERT. CRIM-negative patients mount an immune response to ERT, making this the most dangerous presentation. The following case study describes the 5-year course of the first successful treatment of an in utero CRIM-negative Pompe disease patient with prophylactic immune tolerance induction (ITI) and administration of ERT given within the first 2 days of life followed by ultrasound guided vascular access that facilitated by bi-weekly infusions and extensive phlebotomy.

Pregnancy and associated events in women receiving enzyme replacement therapy for late-onset glycogen storage disease type II (Pompe disease)

2016 ◽  
Vol 42 (10) ◽  
pp. 1263-1271 ◽  
Author(s):  
Philippa J. Rohman ◽  
Elaine Scott ◽  
Linda Richfield ◽  
Uma Ramaswami ◽  
Derralynn A. Hughes
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Storage Disease ◽  
Late Onset ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Ii ◽  
Enzyme Replacement

scholarly journals Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1339
Author(s):  
Naresh K. Meena ◽  
Nina Raben
Keyword(s):  
Pompe Disease ◽  
Specific Treatment ◽  
Lysosomal Storage Diseases ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Monogenic Diseases ◽  
Progressive Accumulation ◽  
Alpha Glucosidase

Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.

Pompe Disease

2016 ◽  
Author(s):  
Ans T. van der Ploeg ◽  
Pascal Laforêt
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Data Gathering ◽  
Autosomal Recessive Disorder ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Walking Distance ◽  
Patient Registries ◽  
Enzyme Replacement ◽  
Progressive Muscle Weakness

Pompe disease, also named acid maltase deficiency and glycogen storage disease type II (GSDII), is a rare autosomal recessive disorder caused by the deficiency of the glycogen-degrading lysosomal enzyme acid α‎-glucosidase. The clinical spectrum of this disease is broad, varying from a lethal infantile-onset generalized myopathy including cardiomyopathy, to late-onset slowly progressive muscle weakness mimicking limb-girdle muscular dystrophy. Respiratory insufficiency is a frequent complication and the main cause of death. The prognosis of Pompe disease has changed considerably with the use of enzyme replacement therapy using recombinant acid α‎-glucosidase (alglucosidase alfa), which has been widely available since 2006. Improvements in survival and major motor achievements can be observed in patients with infantile forms, and recent studies demonstrate improvement of walking distance and stabilization of pulmonary function in late-onset forms. A longer-term study of the safety and efficacy of ERT, based on data gathering across the complete spectrum of Pompe disease via national or international patient registries, is needed in order to formulate more precise guidelines for treatment.

Towards a molecular therapy for glycogen storage disease type II (Pompe disease)

2000 ◽  
Vol 6 (6) ◽  
pp. 245-251 ◽  
Author(s):  
Yuan-Tsong Chen ◽  
Andrea Amalfitano
Keyword(s):  
Glycogen Storage Disease ◽  
Pompe Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Molecular Therapy ◽  
Type Ii

scholarly journals Packaging of an AAV vector encoding human acid α-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector

2003 ◽  
Vol 7 (4) ◽  
pp. 467-477 ◽  
Author(s):  
Baodong Sun ◽  
Y.-T Chen ◽  
Andrew Bird ◽  
Fang Xu ◽  
Yang-Xun Hou ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Ii ◽  
Aav Vector ◽  
Human Acid
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