TY - JOUR
T1 - DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease
AU - Castaldo, Imma
AU - De Rosa, Mariarosaria
AU - Romano, Antonella
AU - Zuchegna, Candida
AU - Squitieri, Ferdinando
AU - Mechelli, Rosella
AU - Peluso, Silvio
AU - Borrelli, Cristiana
AU - Del Mondo, Angelo
AU - Salvatore, Elena
AU - Vescovi, Luigi Angelo
AU - Migliore, Simone
AU - De Michele, Giuseppe
AU - Ristori, Giovanni
AU - Romano, Silvia
AU - Avvedimento, Enrico Vittorio
AU - Porcellini, Antonio
N1 - Funding Information:
This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 16983 to E.V.A.) and the Italian League for Research on Huntington and Related Diseases Foundation (LIRH) Foundation. G.R. and S.R. received funding from the Cure Huntington's Disease Initiative Foundation for collecting patient data and samples on the REGISTRY and ENROLL-HD platforms and from the Italian Government (Ministry of Health). The Italian Ministry of Health supports the research on HD at Scientific Institute for Research and Cure (IRCCS) Casa Sollievo della Sofferenza (funds from Current Research [RC1601MD13] and from Finalized Research [RF-2016-02364123] to F.S. and S.M.). G.R. received funding from Sapienza University of Rome (University Research RM116154EC242C10). The funders of the study had no role in the design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. We thank all patients and their families for participating in this study, and for offering all information, data, and updates on the disease.
Publisher Copyright:
© 2018 American Neurological Association
PY - 2019/2
Y1 - 2019/2
N2 - Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1–6 ANN NEUROL 2019;85:296–301.
AB - Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1–6 ANN NEUROL 2019;85:296–301.
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U2 - 10.1002/ana.25393
DO - 10.1002/ana.25393
M3 - Article
C2 - 30549309
AN - SCOPUS:85059952914
VL - 85
SP - 296
EP - 301
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 2
ER -