作为一种神经退行性疾病，亨廷顿氏病目前没有有效疗法。不过，美国研究人员日前发现一种有望用于“侦测”亨廷顿氏病的生物标记，这将使医生有机会及时了解该病进程并寻找新疗法。
美国马萨诸塞总医院和布里格姆妇科医院的研究人员在新一期美国《国家科学院院刊》网络版上报告说，他们分析了亨廷顿氏病患者、其他神经退行性疾病患者和健康人等共计119名志愿者的血样后发现，与其他人相比，亨廷顿氏病患者血液中表达了更高水平的H2AFY基因，超出普通人水平1.6倍。
研究人员随后通过小鼠实验发现，小鼠和人一样，在受到亨廷顿氏病影响时也会出现H2AFY基因表达水平升高的现象。与未接受治疗的小鼠相比，用神经保护药——苯丁酸钠治疗两周的小鼠，其脑部关键区域的H2AFY基因表达水平降低。
参与研究的科研人员柯莱门斯·舍尔策说：“我们知道如何诊断亨廷顿氏病，但并不掌握简单的‘侦测’方法来了解这种病是否活跃，是否在发展以及是否对新药有反应，这样的‘侦测’对更有效地开展临床研究至关重要，我们对上述新发现所具有的潜力感到激动，下一个挑战是利用这种原型标记物开发用于药物试验的测试方法。”
亨廷顿氏病通常发生在人中年时期，患者症状包括面部和四肢无意识地抽动、心情摇摆不定、健忘，病症随着疾病进程而逐步恶化，患者通常在患病后20年内死亡。（生物谷 Bioon.com)
doi:10.1073/pnas.1104409108
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Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse
Hu, Yi; Chopra, Vanita; Chopra, Raman; Locascio, Joseph J.; Liao, Zhixiang; Ding, Hongliu; Zheng, Bin; Matson, Wayne R.; Ferrante, Robert J.; Rosas, H. Diana; Hersch, Steven M.; Scherzer, Clemens R.
Huntington disease (HD) is a progressive neurodegenerative disease that affects 30,000 individuals in North America. Treatments that slow its relentless course are not yet available, and biomarkers that can reliably measure disease activity and therapeutic response are urgently needed to facilitate their development. Here, we interrogated 119 human blood samples for transcripts associated with HD. We found that the dynamic regulator of chromatin plasticity H2A histone family, member Y (H2AFY) is specifically overexpressed in the blood and frontal cortex of patients with HD compared with controls. This association precedes the onset of clinical symptoms, was confirmed in two mouse models, and was independently replicated in cross-sectional and longitudinal clinical studies comprising 142 participants. A histone deacetylase inhibitor that suppresses neurodegeneration in animal models reduces H2AFY levels in a randomized phase II clinical trial. This study identifies the chromatin regulator H2AFY as a potential biomarker associated with disease activity and pharmacodynamic response that may become useful for enabling disease-modifying therapeutics for HD.
