Neuroprotection in Huntingtons disease:: a 2-year study on minocycline
Neuroprotection in Huntingtons disease:: a 2-year study on minocycline
复制标题
DOI：
10.1097/00004850-200411000-00004
复制
发表时间：
2004-11-01
影响因子：
2.6
通讯作者：
Kapfhammer, HP
中科院分区：
文献类型：
--
作者：
Bonelli, RM;Hödl, AK;Kapfhammer, HP
亨廷顿氏病（HD）是一种持续进行性神经退行性疾病，其临床特征为精神、认知和运动障碍三联征。抗生素米诺环素是一种具有抗凋亡特性的半胱天冬酶抑制剂，已被证明可延长HD转基因小鼠模型的生存期。我们对14例经遗传学证实的HD患者给予米诺环素治疗。在基线时，以及治疗6个月和24个月后，使用统一HD评定量表和神经心理测试组合对患者进行精神病学、神经病学和神经心理学评估。12个月后，3例患者失访，因此在终点时分析了11例患者。米诺环素耐受性良好。与HD的预期自然病程不同，患者在前6个月改善后，在终点时表现出一般运动和神经心理功能的稳定。此外，我们发现精神症状的显着改善在前6个月后并不明显。详细地说，简易精神状态检查、总运动评分、总功能能力量表和独立性量表作为HD中最突出的量表，在治疗3年后稳定。我们的研究结果证实了以前的动物研究，并表明该药物在HD中具有神经保护作用。一项长期、双盲、安慰剂对照试验似乎非常有必要明确确定米诺环素在HD中的价值。(C)2004年利平科特威廉姆斯威尔金斯。
Huntington's disease (HD), a relentlessly progressive neurodegenerative disorder, is characterized by a clinical triad of psychiatric, cognitive and motor disturbances. The antibiotic minocycline, a caspase inhibitor exhibiting antiapoptotic properties, has been shown to prolong survival in the transgenic mouse model of HD. We administrated minocycline to 14 patients with genetically confirmed HD. The patients were psychiatrically, neurologically and neuropsychologically evaluated at baseline, and after 6 and 24 months of treatment, using the Unified HD Rating Scale and a neuropsychological test battery. After 12 months, three patients were lost to follow-up so that 11 patients were analysed at the endpoint. Minocycline was well tolerated. Unlike the expected natural course of HD, patients exhibited stabilization in general motor and neuropsychological function at endpoint, after improving in the first 6 months. Moreover, we found a significant amelioration of psychiatric symptoms that was not apparent after the first 6 months. In detail, the Mini-Mental State Examination, the Total Motor Score, the Total Functional Capacity Scale and the Independence Scale, as the most prominent scales in HD, were stabilized after 3 years of treatment. Our results confirm previous animal studies and indicate a neuroprotective effect of this agent in HD. A long-term, double-blind, placebo-controlled trial appears highly warranted for definitively establishing the value of minocycline in HD. (C) 2004 Lippincott Williams Wilkins.