Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length (TL) and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 pre-manifest, 58 HD patients, with similar CAG expansion in the huntingtin gene (HTT) gene and 44 healthy controls (HC). PBMC from 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 pre-manifest stage of HD, negligible in HC, provides a novel tool to monitor pre-manifest subjects and find patient-specific drugs.
DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease / Castaldo, Imma; De Rosa, Mariarosaria; Romano, Antonella; Zuchegna, Candida; Squitieri, Ferdinando; Mechelli, Rosella; Peluso, Silvio; Borrelli, Cristiana; Del Mondo, Angelo; Salvatore, Elena; Vescovi, Luigi Angelo; Migliore, Simone; De Michele, Giuseppe; Ristori, Giovanni; Romano, Silvia; Avvedimento, Enrico Vittorio; Porcellini, Antonio. - In: ANNALS OF NEUROLOGY. - ISSN 0364-5134. - 85:2(2019), pp. 296-301. [10.1002/ana.25393]
DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease
Mechelli, Rosella;Ristori, Giovanni;Romano, Silvia;
2019
Abstract
Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length (TL) and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 pre-manifest, 58 HD patients, with similar CAG expansion in the huntingtin gene (HTT) gene and 44 healthy controls (HC). PBMC from 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 pre-manifest stage of HD, negligible in HC, provides a novel tool to monitor pre-manifest subjects and find patient-specific drugs.| File | Dimensione | Formato | |
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