Agalsidase

BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disease associated with glycolipid accumulation that impacts multiple physiological systems. We conducted a systematic literature review (SLR) to characterize the humanistic (quality of life [QoL]) and economic burden of FD. METHODS: Searches were conducted in the Embase, MEDLINE® , and MEDLINE® In-Process databases from inception to January 19, 2022. Conference abstracts of specified congresses were manually searched...

Fabry disease, a rare X-linked genetic disorder, results from pathogenic variants in GLA , leading to deficient lysosomal α-galactosidase A enzyme activity and multi-organ manifestations. Since 2001, enzyme replacement therapy (ERT), using agalsidase alfa or agalsidase beta, has been the mainstay treatment, albeit with limitations such as rapid clearance and immunogenicity. Pegunigalsidase alfa, a novel PEGylated recombinant alpha-galactosidase, offers promise as an alternative. Produced in plant cells, pegunigalsidase alfa exhibits enhanced stability, prolonged half-life, and reduced immunogenicity due to pegylation...

Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA)...

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The clinical use of agalsidase alfa as enzyme replacement therapy (ERT) for Fabry disease (FD) has spread since 2001, and a large body of evidence of its effectiveness has been collected. This review presents the clinical and laboratory results achieved with agalsidase alfa, which has been published in the literature. Agalsidase alfa infusion slows down or stops the progression of renal damage, expressed by reduction or stabilization of the annual decline of the glomerular filtration rate; yearly decrease of glomerular filtration rate (slope) sometimes is reduced until its stabilization...

BACKGROUND: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. METHODS AND RESULTS: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10...

No abstract text is available yet for this article.

BACKGROUND/AIM: Fabry disease (FD) is caused by α-galactosidase A (AGA) deficiency, which ultimately leads to the intracellular accumulation of globotriaosylceramide (Gb3). Exosomes play a role in maintaining cellular homeostasis by clearing damaged or toxic materials, including proteins. In the process of excessive accumulation of intracellular Gb3 in Fabry disease, it may be suggested that exosomal secretion of Gb3 increases to preserve cell homeostasis. This study sought to determine how exosomal secretion and cell signaling change in an FD cell model produced by gene silencing...

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD...

Fabry disease is a rare genetic disease caused by a deficiency of α-galactosidase A gene (α-Gal A). Two intravenous enzymes administered every two weeks, agalsidase alfa and beta can slow disease progression and increase survival if administered early, before organ damage occurs. In this case report, we present a patient with a history of anaphylaxis to agalsidase beta who was successfully treated with agalsidase alfa.

BACKGROUND: Fabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking...

Defective α-galactosidase A (AGAL/GLA) due to missense or nonsense mutations in the GLA gene results in accumulation of the glycosphingolipids globotriaosylceramide (Gb3) and its deacylated derivate globotriaosylsphingosine (lyso-Gb3) in cells and body fluids. The aberrant glycosphingolipid metabolism leads to a progressive lysosomal storage disorder, i. e. Fabry disease (FD), characterized by chronic inflammation leading to multiorgan damage. Enzyme replacement therapy (ERT) with agalsidase-alfa or -beta is one of the main treatment options facilitating cellular Gb3 clearance...

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and β or pharmacological oral chaperone migalastat...

We aimed to analyze the clinical data of 10 patients (6 male and 4 female) with Fabry disease (FD). The mean age of the patients was (28.80±9.27) years. Seven patients had classical FD and three had delayed onset FD. Among the 10 patients, six had skin involvement and cutaneous angiokeratoma; five had hypohidrosis or anhidrosis; nine had intermittent neuralgia; and three had supraorbital ridge protrusion, forehead bulge, and lip thickening. Five patients had proteinuria, including one with chronic kidney disease stage 3 and one with chronic kidney disease stage 5...

Fabry disease is an X-linked hereditary disorder caused by deficient α-galactosidase A (GLA) activity. Patients with Fabry disease are often treated with enzyme replacement therapy (ERT). However, ERT often induces the formation of neutralizing antidrug antibodies (ADAs), which may impair the therapeutic efficacy. Here, we report the case of a 32-year-old man with Fabry disease and resultant neutralizing ADAs who was treated by switching from agalsidase-α to agalsidase-β. We monitored biomarkers, such as plasma globotriaosylsphingosine (lyso-Gb3), urinary globotriaosylceramide (Gb3), urinary mulberry bodies, renal and cardiac parameters, and disease severity during the treatment period...

Fabry disease (FD) is a multi-organ disorder caused by a deficiency of alpha-galactosidase (α-GLA) or reduced activity of the enzyme due to mutations in the GLA gene on the X chromosome, making it an X-linked hereditary disease. A 37-year-old man previously diagnosed with sudden deafness and cardiac hypertrophy was referred to our department after an abnormal urine finding during a public health checkup. A renal biopsy revealed characteristic findings, and he was diagnosed with FD with a novel GLA abnormality (c...

AIMS: Cardiomyopathy in Fabry disease (FD) is a major determinant of morbidity and mortality. This study investigates the effects of FD-specific treatment using enzyme replacement therapy (ERT) and chaperone therapy on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE). METHODS AND RESULTS: In this prospective observational single-center study, 20 FD patients [10 (50%) females] treated with migalastat, 48 FD patients [24 (50%) females] treated with ERT (agalsidase-alfa and agalsidase-beta), and 30 untreated FD patients (all females) as controls were analyzed...

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2 /year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years...

AIMS: Cardiac left ventricular hypertrophy (LVH) is the most common manifestation of heart involvement in Anderson-Fabry disease (AFD). Conventional cardiac imaging is not sensitive enough to detect early signs of LVH in AFD. It remains uncertain whether enzyme replacement therapy (ERT) can prevent LVH progression and improve myocardial function. This study aimed to assess the effectiveness of two-dimensional speckle tracking echocardiography (2D-STE) in early detection of cardiac involvement in AFD and monitoring the efficacy of agalsidase alfa and agalsidase beta therapy...

BACKGROUND: Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD). OBJECTIVE/METHODS: BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years...