The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.
Bibliographical noteFunding Information:
Financial support was provided by Sanofi, Pfizer Inc., and the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), and the National Center for Advancing Translational Sciences (NCATS). This consortium is funded through a collaboration between NCATS, NINDS, and NIDDK. Research reported in this publication was also supported by the NCATS Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
S.A.S., M.R.T., K.D.R. report no financial disclosures and conflict of interest in reference to this work. R.V.K. and J.C.C. have received investigator-initiated funds from Pfizer Inc., Sanofi, and the NIH.
© 2022 by the authors.
- Gaucher disease
- oxidative stress
PubMed: MeSH publication types
- Journal Article