Runne Heike, Kuhn Alexandre, Wild Edward J, Pratyaksha Wirahpati, Kristiansen Mark, Isaacs Jeremy D, Régulier Etienne, Delorenzi Mauro, Tabrizi Sarah J, Luthi-Carter Ruth
Laboratory of Functional Neurogenomics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14424-9. doi: 10.1073/pnas.0703652104. Epub 2007 Aug 27.
Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease-modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared with controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, et al. (2005) Proc Natl Acad Sci USA 102:11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies.
对于神经退行性疾病而言,在迫切寻求疾病修正疗法的过程中,高度定量的生物标志物仍然是一项重要需求。对于亨廷顿舞蹈症(HD),已有基因检测方法(性状标志物),但必要的状态标志物仍在研发中。在本报告中,我们描述了一系列作为状态生物标志物候选物进行探索的转录组检测。为了利用已知的疾病神经炎症和转录扰动,我们测量了外周血细胞中的相关mRNA。这些潜在标志物的整体表现较弱,只有一种mRNA,即立即早期反应3(IER3),与对照组相比,在HD样本中显示出适度但显著的32%的增加。对于所测试的任何其他mRNA,包括先前报告中鉴定的一组12种RNA生物标志物[Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV等人(2005年)《美国国家科学院院刊》102:11023 - 11028],均未发现统计学上的显著差异。尽管如此,目前的结果可能会为HD生物标志物策略的未来设计和测试提供参考。