Title Long- and short-term glucosphingosine (lyso-Gb1) dynamics in Gaucher patients undergoing enzyme replacement therapy /
Authors Dubiela, Pawel ; Szymanska-Rozek, Paulina ; Hasinski, Piotr ; Lipinski, Patryk ; Kleinotienė, Gražina ; Giersz, Dorota ; Tylki-Szymanska, Anna
DOI 10.3390/biom14070842
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Is Part of Biomolecules.. Basel : MDPI. 2024, vol. 14, iss. 7, art. no. 842, p. [1-10].. eISSN 2218-273X
Keywords [eng] biomarker ; enzyme replacement therapy ; Gaucher disease ; glucosylsphingosine ; lyso-Gb1
Abstract [eng] Background: Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the GBA1 gene, leading to β-glucocerebrosidase deficiency and glucosylceramide accumulation. Methods: We analyzed short- and long-term dynamics of lyso-glucosylceramide (lyso-Gb1) in a large cohort of GD patients undergoing enzyme replacement therapy (ERT). Results: Eight-years analysis of lyso-Gb1 revealed statistically insignificant variability in the biomarker across the years and relatively high individual variability in patients’ results. GD type 1 (GD1) patients exhibited higher variability compared to GD type 3 (GD3) patients (coefficients of variation: 34% and 23%, respectively; p-value = 0.0003). We also investigated the short-term response of the biomarker to enzyme replacement therapy (ERT), measuring lyso-Gb1 right before and 30 min after treatment administration. We tested 20 GD patients (16 GD1, 4 GD3) and observed a rapid and significant reduction in lyso-Gb1 levels (average decrease of 17%; p-value < 0.0001). This immediate response reaffirms the efficacy of ERT in reducing substrate accumulation in GD patients but, on the other hand, suggests the biomarker’s instability between the infusions. Conclusions: These findings underscore lyso-Gb1’s potential as a reliable biomarker for monitoring efficacy of treatment. However, individual variability and dry blood spot (DBS) testing limitations urge a further refinement in clinical application. Our study contributes valuable insights into GD patient management, emphasizing the evolving role of biomarkers in personalized medicine.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2024
CC license CC license description