Abstract
Background
Hutchinson–Gilford progeria syndrome (HGPS) is an ultra-rare, fatal, segmental premature aging syndrome caused by the aberrant lamin A protein, progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease.
Methods
We performed a prospective longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10% of the world’s population at the time) at baseline and on lonafarnib therapy, compared with age- and gender-matched controls using a multi-analyte, microsphere-based immunofluorescent assay.
Results
The mean levels for 23/66 (34.8%) proteins were significantly lower and 7/66 (10.6%) were significantly higher in HGPS samples compared with those in controls (P≤0.05). Six proteins whose concentrations were initially lower normalized with lonafarnib therapy: interleukins 1α, 7, and 13, beta-2 microglobulin, C-reactive protein, and myoglobin. Alpha-2 macroglobulin, a protease inhibitor associated with stroke, was elevated at baseline and subsequently normalized with lonafarnib therapy.
Conclusion
This is the first study to employ a multi-analyte array platform in HGPS. Novel potential biomarkers identified in this study should be further validated by correlations with clinical disease status, especially proteins associated with cardiovascular disease and those that normalized with lonafarnib therapy.
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Acknowledgements
Most importantly, we are grateful to the children with progeria and their families, and to the children who participated as control subjects, for their participation in this study. We thank Lorraine Fast for sample collection and processing. We thank several specialists who assisted with helpful discussions: Stacy Croteau (hematologic disorders), Catherine Gordon (pediatric endocrine disorders), and Marie Gerhard-Herman (cardiovascular disease).
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L.B.G. is the parent of a child who participated in the study. The other authors have no conflict of interest to declare.
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The Progeria Research Foundation Grants PRF-2002-CB and PRFCLIN2007-02.
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Gordon, L., Campbell, S., Massaro, J. et al. Survey of plasma proteins in children with progeria pre-therapy and on-therapy with lonafarnib. Pediatr Res 83, 982–992 (2018). https://doi.org/10.1038/pr.2018.9
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DOI: https://doi.org/10.1038/pr.2018.9
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