作為一種神經(jīng)退行性疾病,，亨廷頓氏病目前沒有有效療法。不過,，美國研究人員日前發(fā)現(xiàn)一種有望用于“偵測”亨廷頓氏病的生物標記,，這將使醫(yī)生有機會及時了解該病進程并尋找新療法。
美國馬薩諸塞總醫(yī)院和布里格姆婦科醫(yī)院的研究人員在新一期美國《國家科學院院刊》網(wǎng)絡版上報告說,，他們分析了亨廷頓氏病患者,、其他神經(jīng)退行性疾病患者和健康人等共計119名志愿者的血樣后發(fā)現(xiàn)，與其他人相比,，亨廷頓氏病患者血液中表達了更高水平的H2AFY基因,，超出普通人水平1.6倍。
研究人員隨后通過小鼠實驗發(fā)現(xiàn),，小鼠和人一樣,，在受到亨廷頓氏病影響時也會出現(xiàn)H2AFY基因表達水平升高的現(xiàn)象。與未接受治療的小鼠相比,，用神經(jīng)保護藥——苯丁酸鈉治療兩周的小鼠,，其腦部關(guān)鍵區(qū)域的H2AFY基因表達水平降低。
參與研究的科研人員柯萊門斯·舍爾策說：“我們知道如何診斷亨廷頓氏病,，但并不掌握簡單的‘偵測’方法來了解這種病是否活躍,，是否在發(fā)展以及是否對新藥有反應，這樣的‘偵測’對更有效地開展臨床研究至關(guān)重要,，我們對上述新發(fā)現(xiàn)所具有的潛力感到激動,，下一個挑戰(zhàn)是利用這種原型標記物開發(fā)用于藥物試驗的測試方法。”
亨廷頓氏病通常發(fā)生在人中年時期,，患者癥狀包括面部和四肢無意識地抽動,、心情搖擺不定、健忘,，病癥隨著疾病進程而逐步惡化,，患者通常在患病后20年內(nèi)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.
