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. 2021 Jan;23(1):192-201.
doi: 10.1038/s41436-020-00968-z. Epub 2020 Sep 30.

Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease

Daniel G Bichet  1 , Johannes M Aerts  2 , Christiane Auray-Blais  3 , Hiroki Maruyama  4 , Atul B Mehta  5 , Nina Skuban  6 , Eva Krusinska  6 , Raphael Schiffmann  7
Affiliations

Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease

Daniel G Bichet et al. Genet Med. 2021 Jan.

Erratum in

Abstract

Purpose: To assess the utility of globotriaosylsphingosine (lyso-Gb3) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat.

Methods: A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)-experienced patients with migalastat-amenable GLA variants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb3 and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb3 and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb3 and kidney interstitial capillary (KIC) globotriaosylceramide (Gb3) inclusions was assessed in treatment-naive patients.

Results: No significant correlations were identified between changes in lyso-Gb3 and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb3 levels nor the rate of change in lyso-Gb3 levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for ≥24 months. Changes in lyso-Gb3 correlated with changes in KIC Gb3 inclusions in treatment-naive patients.

Conclusions: Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb3 may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.

Keywords: Fabry disease; biomarker; clinical monitoring; lyso-Gb3; migalastat.

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Figures

Fig. 1
Fig. 1. Lack of correlation between changes in plasma lyso-Gb3 and changes in LVMi, eGFR, and pain at selected timepoints of migalastat treatment.
(a) Relationship between changes in lyso-Gb3 versus changes in LVMi. (b) Relationship between changes in lyso-Gb3 vs. changes in eGFR. (c) Relationship between changes in lyso-Gb3 versus changes in worst pain in 24 hours. eGFR estimated glomerular filtration rate, ERT enzyme replacement therapy, LVMi left ventricular mass index, lyso-Gb3 globotriaosylsphingosine, OLE open-label extension.
See this image and copyright information in PMC

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