A prospective 10‐year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease

Schiffmann, Raphael; Swift, Caren; Wang, Xuan; Blankenship, Derek; Ries, Markus

doi:10.1007/s10545-015-9845-5

Cited by 36 publications

(38 citation statements)

References 32 publications

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“…A recent study by Germain and colleagues showed that less affected individuals with a better preserved kidney function at baseline benefited from ERT, experiencing better renal and cardiovascular outcomes during the observational period [36]. Moreover, in male FD patients, enhanced therapeutic outcomes may occur if we increase the ERT dose [35, 37, 38], or frequency of infusions [39], in combination with intensified additional medication such as ARBs and ACE inhibitors [16]. In patients with amenable mutations, pharmacological chaperones have been shown as a useful therapeutic alternative [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Nowak¹,

Koch²,

Huynh‐Do³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. Methods: The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 – 54] years for females and 39 [28 – 49] years for males. Results: A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Conclusion: Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function.

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Section: Discussionmentioning

confidence: 99%

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Nowak¹,

Koch²,

Huynh‐Do³

et al. 2017

Kidney Blood Press Res

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“…It is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3) and other related glycolipids sub-types (e.g., glycosphingolipids) in many cell types, including blood vessels throughout the body. This buildup initiates a cascade of events, starting with the disruption of basic metabolic processes at the cellular level and progressing to inflammatory events and cell death, thereby affecting the system as a whole with an increase of renal, cardiac, cerebrovascular, and skin complications [1,2]. …”

Section: Introductionmentioning

confidence: 99%

“…FD management and therapy employs the regular use of agalsidase-alpha (Replagal) and agalsidase-beta (Fabrazyme). They are reported as improvers of renal and cardiac function, and cerebrovascular flow [1,8]. …”

Section: Introductionmentioning

confidence: 99%

Integrative Systems Biology Investigation of Fabry Disease

Fernandes

Husi

2016

Diseases

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Fabry disease (FD) is a rare X-linked recessive genetic disorder caused by a deficient activity of the lysosomal enzyme alpha-galactosidase A (GLA) and is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3). We performed a meta-analysis of peer-reviewed publications including high-throughput omics technologies including naïve patients and those undergoing enzyme replacement therapy (ERT). This study describes FD on a systems level using a systems biology approach, in which molecular data sourced from multi-omics studies is extracted from the literature and integrated as a whole in order to reveal the biochemical processes and molecular pathways potentially affected by the dysregulation of differentially expressed molecules. In this way new insights are provided that describe the pathophysiology of this rare disease. Using gene ontology and pathway term clustering, FD displays the involvement of major biological processes such as the acute inflammatory response, regulation of wound healing, extracellular matrix (ECM) remodelling, regulation of peptidase activity, and cellular response to reactive oxygen species (ROS). Differential expression of acute-phase response proteins in the groups of naïve (up-regulation of ORM1, ORM2, ITIH4, SERPINA3 and FGA) and ERT (down-regulation of FGA, ORM1 and ORM2) patients could be potential hallmarks for distinction of these two patient groups.

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“…Cornea verticillata is the most distinctive clinical ocular finding of Fabry disease (Sher et al 1979;Sodi et al 2006). Enzyme replacement therapy (ERT) has been used for treatment of Fabry disease for over 10 years, and some recent studies have reported the long-term therapeutic efficacy of ERT on cardiac or kidney function over 10 years (Germain et al 2015;Schiffmann et al 2015). While little is known about corneal changes associated with long-term ERT (Fledelius et al 2015), we report a case of marked regression of corneal deposits in a patient with Fabry disease 16 years after ERT.…”

Section: Referencesmentioning

confidence: 91%

Prominent regression of corneal deposits in Fabry disease 16 years after initiation of enzyme replacement therapy

Koh

Sakai

Maeda

et al. 2017

Acta Ophthalmologica

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A prospective 10‐year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease

Abstract: Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

Cited by 36 publications

References 32 publications

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Integrative Systems Biology Investigation of Fabry Disease

Prominent regression of corneal deposits in Fabry disease 16 years after initiation of enzyme replacement therapy

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