Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30μM. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline. Ann Neurol 2003

中文翻译：

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米诺环素和强力霉素对亨廷顿病模型无益

亨廷顿病 (HD) 是一种遗传性神经系统疾病，可导致运动障碍、人格改变、痴呆和过早死亡，目前尚无有效治疗方法。据报道，改良的四环素抗生素米诺环素可改善 HD 的 R6/2 小鼠模型中的疾病表型。因为据报道，四环素类还可以抑制其他淀粉样蛋白疾病的聚集，我们研究了它们抑制亨廷顿蛋白聚集的能力，并进一步探索了它们在临床前小鼠试验中的功效。我们表明，在 30μM 的有效浓度下，四环素是 HD 海马切片培养模型中亨廷顿蛋白聚集的有效抑制剂。然而，尽管通过用米诺环素口服治疗 R6/2 小鼠达到接近该浓度的组织水平，我们观察到他们的行为异常或死后总负荷没有明显差异。鉴于这些新数据，我们建议在进行米诺环素的人体临床试验时要谨慎行事。安·内尔 2003