Agalsidase

Fabry disease is an X-linked inherited lysosomal storage disorder with a deficiency of α-galactosidase A activity, which results in the intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in various organs. Fabry nephropathy is one of the major complications of Fabry disease, and kidney damage is often related to cardiovascular disease and mortality. The treatment of Fabry nephropathy thus helps prolong life expectancy. Two treatment options for Fabry nephropathy and cardiopathy are now commercially available: enzyme replacement therapy (agalsidase α agalsidase β, and a biosimilar of agalsidase β) and pharmacological chaperone therapy (migalastat)...

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BACKGROUND: Agalsidase beta, an enzyme replacement therapy for Fabry disease, is dosed biweekly at 1 mg/kg body weight, with increasing infusion rates based on tolerability. The US label specifies ≥ 90-min infusions for all patients; the US and EU labels require ≤ 15 mg/hr infusions in patients < 30 kg. The Japanese label allows infusions up to 30 mg/hr, allowing < 90-min dosing for some patients weighing < 45 kg...

Fabry disease (FD, α-galactosidase A deficiency) is a rare, progressive, complex lysosomal storage disorder affecting multiple organ systems with a diverse spectrum of clinical phenotypes, particularly among female patients. Knowledge of its clinical course was still limited in 2001 when FD-specific therapies first became available and the Fabry Registry (NCT00196742; sponsor: Sanofi) was initiated as a global observational study. The Fabry Registry has now been operational for over 20 years, overseen by expert Boards of Advisors, and has collected real-world demographic and longitudinal clinical data from more than 8000 individuals with FD...

Fabry disease is an X-linked lysosomal storage disorder caused by defective enzyme activity of α-galactosidase A and treated with enzyme replacement therapy (ERT) with recombinant α-galactosidase. ERT reduces left ventricular mass assessed by echocardiography or magnetic resonance imaging. However, electrocardiogram changes during ERT have not been fully elucidated. In the present case, ERT with agalsidase alfa for 4 years decreased QRS voltage and negative T depth along with a reduction of left ventricular mass and wall thickness and improvement of symptoms in a female patient with Fabry disease...

A review was conducted to evaluate interventional therapy for Fabry disease. Fabry disease is a multisystemic X-linked storage disorder that affects the entire body and needs to be treated at an early age. The search was conducted using keywords such as "Fabry disease" and "Management" to review the databases. Seven studies were chosen from the 90 studies, and it was discovered that migalastat and enzyme replacement medication were successful in treating the condition, whereas agalsidase beta failed to have a positive effect on the patient...

BACKGROUND AND OBJECTIVE: Fabry disease (FD) is a rare lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (aGal A). Since 2001, two different enzyme replacement therapies have been authorized, with agalsidase beta being used in most parts of the Western world. Currently, biosimilars of several expensive enzyme therapies are under development to improve their accessibility for patients. We present the preclinical results of the development of a biosimilar to agalsidase beta...

Enzyme replacement therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, the treatment has side effects, is costly, and requires conspicuous amounts of recombinant human protein (rh-AGAL). Thus, its optimization would benefit patients and welfare/health services (i.e., society at large). In this brief report, we describe preliminary results paving the way for two possible approaches: i. the combination of enzyme replacement therapy with pharmacological chaperones; and ii...

OBJECTIVE: This article analyzes the data of four families with mutations of the GLA (galactosidase) gene with a special focus on the clinical presentation, diagnosis, and interdisciplinary clinical management of Fabry disease (FD) and enzyme replacement therapy (ERT) treatment, and has the aim to assess more accurate prevention and treatment strategy. METHODS: The MSSI (Mainz Severity Score Index) scale was used to evaluate the clinical data of five children diagnosed in our hospital, and the genotypes of all the patients with FD were collected...

Fabry disease is a lysosomal storage disorder caused by the deficiency of the α-galactosidase-A enzyme. The result is the progressive accumulation of complex glycosphingolipids and cellular dysfunction. Cardiac, renal, and neurological involvement significantly reduces life expectancy. Currently, there is increasing evidence that clinical response to treatment improves with early and timely initiation. Until a few years ago, treatment options for Fabry disease were limited to enzyme replacement therapy with agalsidase alfa or beta administered by intravenous infusion every 2 weeks...

BACKGROUND: Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing. OBJECTIVES: We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents...

OBJECTIVE: To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children. METHODS: The clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed. RESULTS: Among the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age...

BACKGROUND: Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). METHODS: Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database...

Enzyme replacement therapy (ERT) with recombinant α-galactosidase A (AGAL) can lead to the formation of neutralizing anti-drug antibodies (ADA), which significantly limit treatment efficacy in patients with Fabry disease (FD). The effects of dose escalation on ADA titer and plasma globotriaosylsphingosine (lyso-Gb3 ) level are unknown. We screened 250 FD patients (200 males, 50 females) under ERT for ADAs and assessed the impact of an approved dose escalation in affected patients, focusing on ADA titers and plasma lyso-Gb3 ...

Recently, a new mechanism of drug-drug interaction (DDI) was reported between agalsidase, a therapeutic protein, and migalastat, a small molecule, both of which are treatment options of Fabry disease. Migalastat is a pharmacological chaperone that stabilizes the native form of both endogenous and exogenous agalsidase. In Fabry patients co-administrated with agalsidase and migalastat, the increase in active agalsidase exposure is considered a pharmacokinetic effect of agalsidase infusion but a pharmacodynamic effect of migalastat administration, which makes this new DDI mechanism even more interesting...

Fabry disease (FD) is a rare lysosomal storage disorder, characterized by a reduction in α-galactosidase A enzyme activity and the progressive accumulation of globotriaosylceramide (GL3) and its metabolites in the cells of various organs. Agalsidase beta, an enzyme replacement therapy (ERT), is approved for use in patients with FD in Europe, Canada, Australia, South America, and Asia, and is the only ERT approved for use in the United States. In this review, we discuss the clinical relevance of GL3 accumulation, the effect of agalsidase beta on GL3 in target tissues, and the association between treatment-related tissue GL3 clearance and long-term structure, function, or clinical outcomes...

We monitored anti-drug antibodies and disease-specific biomarkers in three patients with a nonsense mutation from a Japanese Fabry family treated with enzyme replacement therapy (ERT). In two male patients from the family, neutralizing anti-drug antibodies were induced at an early stage of ERT, the antibody titer peak being found at an earlier stage of ERT in the patient treated with 1.0 mg/kg agalsidase beta than in that treated with 0.2 mg/kg agalsidase alfa. Then, the antibody titers decreased with continuation of ERT...

Fabry disease (FD) is a rare, X-linked inherited lysosomal storage disorder, characterized by the accumulation of globotriaosylceramide (Gb3) due to the deficiency or absence of alpha-galactosidase A. Due to the accumulation of Gb3, cardiac, renal, neurological, and skin manifestations can be observed. Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta is the cornerstone in the management of FD. Both enzymes are clinically effective and widely used. In this study, we present a 19-year-old male patient with FD who had received ERT for almost two and half years without any complications...

UNLABELLED: Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120)...

BACKGROUND: The efficacy of enzyme replacement therapy (ERT) in mobilizing globotryaosylceramide (GB-3) from Fabry cardiomyocytes is limited. The mechanism involved is still obscure. METHODS: Assessment of M6Pr, M6Pr-mRNA, and Ubiquitin has been obtained by Western blot analysis and real-time PCR of frozen endomyocardial biopsy samples, from 17 pts with FD, various degree of left ventricular hypertrophy, and maximal wall thickening (MWT) from 11.5 and 20 mm. The diagnosis and severity of FDCM followed definitions of GLA mutation, α-galactosidase A enzyme activity, cardiac magnetic resonance, and left ventricular endomyocardial biopsy with the quantification of myocyte hypertrophy and the extent of Gb-3 accumulation...