scholarly journals Determination of Acid α-Glucosidase Protein: Evaluation as a Screening Marker for Pompe Disease and Other Lysosomal Storage Disorders

2000 ◽  
Vol 46 (9) ◽  
pp. 1318-1325 ◽  
Author(s):  
Kandiah Umapathysivam ◽  
Alison M Whittle ◽  
Enzo Ranieri ◽  
Colleen Bindloss ◽  
Elaine M Ravenscroft ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Screening Program ◽  
Dried Blood Spots ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Total Acid ◽  
Blood Spots ◽  
Enzyme Replacement ◽  
Storage Disorders

Abstract Background: In recent years, there have been significant advances in the development of enzyme replacement and other therapies for lysosomal storage disorders (LSDs). Early diagnosis, before the onset of irreversible pathology, has been demonstrated to be critical for maximum efficacy of current and proposed therapies. In the absence of a family history, the presymptomatic detection of these disorders ideally can be achieved through a newborn screening program. One approach to the development of such a program is the identification of suitable screening markers. In this study, the acid α-glucosidase protein was evaluated as a marker protein for Pompe disease and potentially for other LSDs. Methods: Two sensitive immunoquantification assays for the measurement of total (precursor and mature) and mature forms of acid α-glucosidase protein were used to determine the concentrations in plasma and dried blood spots from control and LSD-affected individuals. Results: In the majority of LSDs, no significant increases above control values were observed. However, individuals with Pompe disease showed a marked decrease in acid α-glucosidase protein in both plasma and whole blood compared with unaffected controls. For plasma samples, this assay gave a sensitivity of 95% with a specificity of 100%. For blood spot samples, the sensitivity was 82% with a specificity of 100%. Conclusions: This study demonstrates that it is possible to screen for Pompe disease by screening the concentration of total acid α-glucosidase in plasma or dried blood spots.

scholarly journals Reliability of enzyme assays in dried blood spots for diagnosis of 4 lysosomal storage disorders

2011 ◽  
Vol 01 (03) ◽  
pp. 58-64 ◽  
Author(s):  
Romina Ceci ◽  
Pablo N. de Francesco ◽  
Juan M. Mucci ◽  
Lorena N. Cancelarich ◽  
Carlos A. Fossati ◽  
...  
Keyword(s):  
Dried Blood Spots ◽  
Lysosomal Storage Disorders ◽  
Enzyme Assays ◽  
Lysosomal Storage ◽  
Blood Spots ◽  
Storage Disorders

scholarly journals FDA orphan drug designations for lysosomal storage disorders – a cross sectional analysis

2020 ◽  
Author(s):  
Sven F. Garbade ◽  
Matthias Zielonka ◽  
Konstantin Mechler ◽  
Stefan Kölker ◽  
Georg F. Hoffmann ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Small Molecules ◽  
Orphan Drug ◽  
Pompe Disease ◽  
Gaucher Disease ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps I ◽  
Storage Disorders

AbstractPurposeTo provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat lysosomal storage disorders (LSD’s).MethodsAssessment of the drug pipeline through analysis of the FDA database for orphan drug designations with descriptive and comparative statistics.ResultsBetween 1983 and 2019, 124 orphan drug designations were granted by the FDA for compounds intended to treat 28 lysosomal storage diseases. Orphan drug designations focused on Gaucher disease (N=16), Pompe disease (N=16), Fabry disease (N=10), MPS II (N=10), MPS I (N=9), and MPS IIIA (N=9), and included enzyme replacement therapies, gene therapies, and small molecules, and others. Twenty-three orphan drugs were approved for the treatment of 11 LSDs. Gaucher disease (N=6), cystinosis (N=5), Pompe disease (N=3), and Fabry disease (N=2) had multiple approvals, CLN2, LAL-D, MPS I, II, IVA, VI, and VII one approval each. This is an increase of nine more approved drugs and four more treatable LSD’s (CLN2, MPS VII, LAL-D, and MPS IVA) since 2013. Mean time between orphan drug designation and FDA approval was 89.7 SD 55.00 (range 8-203, N=23) months.ConclusionsThe development pipeline is growing and evolving into diversified small molecules and gene therapy. CLN2 was the first and only LSD with an approved therapy directly targeted to the brain. Newly approved products included “me-too” – enzymes and innovative compounds such as the first pharmacological chaperone for the treatment of Fabry disease.

scholarly journals Determination of Acid α-Glucosidase Activity in Blood Spots as a Diagnostic Test for Pompe Disease

2001 ◽  
Vol 47 (8) ◽  
pp. 1378-1383 ◽  
Author(s):  
Kandiah Umapathysivam ◽  
John J Hopwood ◽  
Peter J Meikle
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Dried Blood Spots ◽  
Cultured Fibroblasts ◽  
Virtual Absence ◽  
Screening Programs ◽  
Blood Spots ◽  
Enzyme Replacement ◽  
Glucosidase Activity

Abstract Background: Pompe disease is an autosomal recessive disorder of glycogen metabolism that is characterized by a deficiency of the lysosomal acid α-glucosidase. Enzyme replacement therapy for the infantile and juvenile forms of Pompe disease currently is undergoing clinical trials. Early diagnosis before the onset of irreversible pathology is thought to be critical for maximum efficacy of current and proposed therapies. In the absence of a family history, the presymptomatic detection of these disorders ideally can be achieved through a newborn-screening program. Currently, the clinical diagnosis of Pompe disease is confirmed by the virtual absence, in infantile onset, or a marked reduction, in juvenile and adult onset, of acid α-glucosidase activity in muscle biopsies and cultured fibroblasts. These assays are invasive and not suited to large-scale screening. Methods: A sensitive immune-capture enzyme activity assay for the measurement of acid α-glucosidase protein was developed and used to determine the activity of this enzyme in dried-blood spots from newborn and adult controls, Pompe-affected individuals, and obligate heterozygotes. Results: Pompe-affected individuals showed an almost total absence of acid α-glucosidase activity in blood spots. The assay showed a sensitivity and specificity of 100% for the identification of Pompe-affected individuals. Conclusions: The determination of acid α-glucosidase activity in dried-blood spots is a useful, noninvasive diagnostic assay for the identification of Pompe disease. With further validation, this procedure could be adapted for use with blood spots collected in newborn-screening programs.

Rapid diagnostic testing procedures for lysosomal storage disorders: α-glucosidase and β-galactosidase assays on dried blood spots

2009 ◽  
Vol 402 (1-2) ◽  
pp. 38-41 ◽  
Author(s):  
Nicoletta Gasparotto ◽  
Rosella Tomanin ◽  
Anna Chiara Frigo ◽  
Gabriela Niizawa ◽  
Elisabetta Pasquini ◽  
...  
Keyword(s):  
Diagnostic Testing ◽  
Dried Blood Spots ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Rapid Diagnostic Testing ◽  
Testing Procedures ◽  
Blood Spots ◽  
Storage Disorders

scholarly journals A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Atul Mehta ◽  
Uma Ramaswami ◽  
Joseph Muenzer ◽  
Roberto Giugliani ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Clinical Manifestations ◽  
Lysosomal Storage Disorders ◽  
Expert Committee ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Access Program ◽  
Storage Disorders

Abstract Background Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

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