Global Incidence and Prevalence of Gaucher Disease: A Targeted Literature Review

Castillon, Genaro; Chang, Shun-Chiao; Moride, Yola

doi:10.3390/jcm12010085

Cited by 15 publications

(6 citation statements)

References 55 publications

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“…Given ABX’s over-the-counter availability and oral formulation, its effectiveness for certain GD manifestations could offer significant benefits, particularly for patients encountering challenges with their current treatment regimens, especially those with neurological symptoms. Although they have a lower prevalence, the nGD subtypes are more prevalent in developing countries of the middle east and Ascia-Pacfic ( Al-Jasmi et al, 2013 ; Roshan Lal and Sidransky, 2017 ; Fateen and Abdallah, 2019 ; Castillon et al, 2022 ). Providing a cheaper therapeutic option like ABX can solve the limited availability of ERT and SRT expensive medications to this group of patients.…”

Section: Ambroxol As a Potential Pharmacological Chaperone Therapy In Gdmentioning

confidence: 99%

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies

Mohamed,

Al-Jasmi

2024

Front. Pharmacol.

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Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of different GBA1 genotypes. The variability in response to ABX varies across different variants, highlighting the diversity in patients’ therapeutic outcomes. Its oral availability and safety profile make it an attractive option, particularly for patients with neurological manifestations. Clinical trials are essential to explore further ABX’s potential as a therapeutic medication for GD to encourage pharmaceutical companies’ investment in its development. This review highlights the potential of ABX as a pharmacological chaperone therapy for GD and stresses the importance of addressing response variability in clinical studies to improve the management of this rare and complex disorder.

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Section: Ambroxol As a Potential Pharmacological Chaperone Therapy In Gdmentioning

confidence: 99%

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies

Mohamed,

Al-Jasmi

2024

Front. Pharmacol.

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“…Gaucher disease is inherited in an autosomal recessive manner and is due to the deficiency of beta-glucocerebrosidase, caused by pathogenic changes in the GBA gene. The estimated incidence of Gaucher disease is 0.39-5.80/100,000 [35], but the prevalence in the Ashkenazi Jewish population is higher with 1/450 being affected [36]. Deficiency of beta-glucocerebrosidase results in accumulation of the substrate glucocerebroside (GL1).…”

Section: Gaucher Diseasementioning

confidence: 99%

Overview of Newborn Screening of Lysosomal Storage Diseases for Pediatric Care Providers

Lahr,

Henderson,

Williams

et al. 2023

OBM Genet

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Lysosomal storage disorders (LSD) are caused by enzymatic failure to degrade specific cellular byproducts of metabolism within the lysosome. They have a wide range of presentations involving multiple body systems and can manifest from infancy through adulthood. As treatments have become available for many of these disorders, newborn screening has been adapted for early identification and pre-symptomatic treatment. This article will review some of the LSD that are now being added to newborn screening panels, including globoid cell leukodystrophy (Krabbe), Gaucher disease, Fabry disease, Mucopolysaccharidosis Type I (Hurler; MPSI), Mucopolysaccharidosis Type II (Hunter; MPSII), Acid Sphingomyelinase deficiency (ASMD), and Pompe disease.

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“…Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) of glycosphingolipids. It occurs at a frequency of 1 in 100,000 live births in the general population and of 1 in 450 live births among Ashkenazi Jews [ 1 , 2 ]. GD is caused by mutations in the GBA gene (mapped on chromosome 1q21-22), which encodes for the lysosomal enzyme acid β-glucosidase (glucocerebrosidase, also known as GCase and GBA, EC 3.2.1.45, MIM*606463).…”

Section: Introductionmentioning

confidence: 99%

Identification of GM1-Ganglioside Secondary Accumulation in Fibroblasts from Neuropathic Gaucher Patients and Effect of a Trivalent Trihydroxypiperidine Iminosugar Compound on Its Storage Reduction

Ceni,

Clemente,

Mangiavacchi

et al. 2024

Molecules

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Gaucher disease (GD) is a rare genetic metabolic disorder characterized by a dysfunction of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) due to mutations in the gene GBA1, leading to the cellular accumulation of glucosylceramide (GlcCer). While most of the current research focuses on the primary accumulated material, lesser attention has been paid to secondary storage materials and their reciprocal intertwining. By using a novel approach based on flow cytometry and fluorescent labelling, we monitored changes in storage materials directly in fibroblasts derived from GD patients carrying N370S/RecNcil and homozygous L444P or R131C mutations with respect to wild type. In L444P and R131C fibroblasts, we detected not only the primary accumulation of GlcCer accumulation but also a considerable secondary increase in GM1 storage, comparable with the one observed in infantile patients affected by GM1 gangliosidosis. In addition, the ability of a trivalent trihydroxypiperidine iminosugar compound (CV82), which previously showed good pharmacological chaperone activity on GCase enzyme, to reduce the levels of storage materials in L444P and R131C fibroblasts was tested. Interestingly, treatment with different concentrations of CV82 led to a significant reduction in GM1 accumulation only in L444P fibroblasts, without significantly affecting GlcCer levels. The compound CV82 was selective against the GCase enzyme with respect to the β-Galactosidase enzyme, which was responsible for the catabolism of GM1 ganglioside. The reduction in GM1-ganglioside level cannot be therefore ascribed to a direct action of CV82 on β-Galactosidase enzyme, suggesting that GM1 decrease is rather related to other unknown mechanisms that follow the direct action of CV82 on GCase. In conclusion, this work indicates that the tracking of secondary storages can represent a key step for a better understanding of the pathways involved in the severity of GD, also underlying the importance of developing drugs able to reduce both primary and secondary storage-material accumulations in GD.

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Global Incidence and Prevalence of Gaucher Disease: A Targeted Literature Review

Cited by 15 publications

References 55 publications

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies

Overview of Newborn Screening of Lysosomal Storage Diseases for Pediatric Care Providers

Identification of GM1-Ganglioside Secondary Accumulation in Fibroblasts from Neuropathic Gaucher Patients and Effect of a Trivalent Trihydroxypiperidine Iminosugar Compound on Its Storage Reduction

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