Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents

Ries, Markus; Clarke, Joe T.R.; Whybra, Catharina; Mehta, Atul; Loveday, Kenneth S.; Brady, Roscoe O.; Beck, Michael; Schiffmann, Raphael

doi:10.1177/0091270007305299

Cited by 41 publications

(47 citation statements)

References 32 publications

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“…It has been proved that enzyme replacement therapy (ERT) to be the most effective therapy in reducing Gb 3 level in FD if administered before prolonged accumulation (Germain et al 2007;Banikazemi et al 2007). Agalsidase alpha and agalsidase beta have been developed for the treatment of FD, and cleared up accumulation of Gb 3 in the blood vessels, kidney, skin, and heart cells in FD (Ries et al 2007). ERT is administered before initiation of clinical signs and symptoms for male classic FD.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

et al. 2016

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

et al. 2016

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“…1,2 In addition, the measurement of plasma Gb 3 concentration was used as a pharmacodynamic marker to demonstrate the biological activity of agalα in vivo. 20 For patients with elevated plasma or urine Gb 3 concentrations before treatment, ERT resulted in an initial drop in Gb 3 concentrations. 7,8 Lower Gb 3 concentrations did not always coincide with clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Schiffmann¹,

Ries

Blankenship

et al. 2013

Genetics in Medicine

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Original research articleGlobotriaosylceramide (Gb 3 ) is often elevated in the urine of patients with Fabry disease, 1 and some studies support its use as a diagnostic biomarker. [2][3][4] Plasma Gb 3 concentration has been found to be consistently elevated in hemizygous males with classic Fabry disease but variably elevated in some variant hemizygous males with residual enzyme activity and in heterozygous females. 5,6 No evidence has been published supporting the use of plasma or urine Gb 3 concentrations as a biomarker for disease progression or response to treatment. For patients with elevated plasma or urine Gb 3 concentrations before treatment, enzyme replacement therapy (ERT) results in an initial drop in Gb 3 concentrations. 5,7 The lower Gb 3 concentrations do not remain low in all patients and do not always coincide with clinical improvement. 8 Biomarkers are generally defined as measurements that reflect the activity of a disease process 9 and can be (i) prognostic, (ii) predictive, or (iii) pharmacodynamic. 10 The goal of this study was to assess the relationship of plasma and urine Gb 3 concentrations with renal or cardiac outcome measures. A previous analysis of pooled data from three randomized, placebo-controlled clinical trials and their open-label extensions (sponsored by Shire Human Genetic Therapies) of male patients with Fabry disease suggested a stabilizing effect of agalsidase alfa (agalα) on renal function assessed by measured glomerular filtration rate (GFR). 11 In that analysis, baseline GFR or elevated proteinuria category (≥1 g/24 h) significantly predicted GFR decline during treatment. Using a suitable selection approach of pooled data Purpose: Globotriaosylceramide concentrations were assessed as potential predictors of change from baseline after 12 months by estimated glomerular filtration rate and left-ventricular mass index using pooled data from three randomized, placebo-controlled agalsidase alfa trials and open-label extensions of patients with Fabry disease.Methods: Males (aged 18 years or older) with Fabry disease received agalsidase alfa (0.2 mg/kg every other week for 12 months). A backward-elimination approach evaluated potential predictors (baseline estimated glomerular filtration rate and left-ventricular mass index; age at first dose; baseline and change from baseline at 12 months of globotriaosylceramide (urine, plasma); urine protein excretion; and systolic and diastolic blood pressure). Subgroups included patients randomized to placebo or agalsidase alfa (double-blind phase), then to agalsidase alfa (open-label extensions; placebo→agalsidase alfa or agalsidase alfa→agalsidase alfa, respectively) and stage 2/3 chronic kidney disease patients.Results: Baseline estimated glomerular filtration rate, age at first dose, baseline urine globotriaosylceramide excretion, and baseline and change from baseline urine protein excretion significantly predicted change from baseline estimated glomerular filtration rate in the analysis population (N = 73; all P<0.05), although not in...

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“…Proteinürik dönemde tanı konulan hastalara ACE inhibitörleri ve ARB verilebilir (8). Enzim replasman tedavisi (ERT)'nin Gb-3'ün kan damarlarında, böbrek, cilt ve kalp hücrelerinde birikimi temizlediği gösterilmiştir (9). Klinik olarak ERT, böbrek fonksiyonlarını stabilize eder, kardiyak kitleyi azaltır ve yaşam kalitesinde belirgin bir iyileşme sağlar (10).…”

Section: Discussionunclassified

Son dönem böbrek yetmezliğinin nadir bir nedeni: Fabry hastalığı

Esen¹,

Atay²,

Gökmen³

et al. 2015

Ege Tıp Dergisi

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ÖzFabry hastalığı, Gaucher hastalığından sonra, ikinci en sık lizozomal depo hastalığıdır. Sistemik olarak pek çok bulgu vermesine rağmen teşhisi genellikle gecikmektedir. Benzer hastalık bulguları olan aile öyküsü, tanı için önemlidir. Bu yazıda, mitral yetmezlliği ve kardiyomyopati mevcut olup son dönem böbrek yetmezliği nedeniyle hemodiyaliz uygulanan ve genetik analiz sonucu Fabry hastalığı tanısı konulan 23 yaşında erkek hasta sunulmaktadır.Anahtar Sözcükler: Fabry hastalığı, hemodiyaliz, son dönem böbrek yetmezliği. Abstract Fabry disease is the second most common lysosomal storage disease after Gaucher disease. Although there are many systemic symptoms, generally diagnosis of Fabry disease is delayed. Having a family history of Fabry disease with symptoms is important for diagnosis. In this report, a 23-year-old male patient diagnosed as Farby disease by genetic analysis is presented who had mitral insufficiency, cardiomyopathy and end stage renal failure requiring hemodialysis.

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Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents

Cited by 41 publications

References 32 publications

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Son dönem böbrek yetmezliğinin nadir bir nedeni: Fabry hastalığı

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