來自美國賓夕法尼亞大學(xué)醫(yī)學(xué)院的研究人員在2012年阿爾茨海默病協(xié)會主辦的國際會議上報道,，一種被稱作epithilone D(EpoD)的tau抗體藥物能夠有效地在動物模型中防治阿爾茨海默病的發(fā)展，改善神經(jīng)元功能和認知，同時降低tau病理特征,。
通過靶向tau，這種抗體藥物旨在讓微管保持穩(wěn)定，從而有助于促進必需營養(yǎng)物質(zhì)和信息在細胞之間進行傳輸,。當tau不起作用時，微管破裂,，而且tau堆積而形成纖維纏結(jié),。賓夕法尼亞大學(xué)佩雷爾曼醫(yī)學(xué)院病理學(xué)與臨床醫(yī)學(xué)教授John Trojanowski博士說，“在動物模型中,，這種藥物通過矯正tau功能喪失從而讓微管保持穩(wěn)定和彌補因形成神經(jīng)原纖維纏結(jié)(neurofibrillary tangle)而造成的tau丟失,，這就表明該藥物有效地攻擊靶標tau，同時還提示著調(diào)控阿爾茨海默病和其他基于tau 的神經(jīng)退化疾病中的tau功能將可能成為一種重要的治療選擇。除了靶向淀粉樣蛋白的藥物---它們可能在晚期阿爾茨海默病中不能發(fā)揮作用---之外,，我們希望這種藥物和其他tau抗體藥物能夠在阿爾茨海默病患者體內(nèi)進行測試以便確定讓發(fā)生功能障礙的tau蛋白破壞的微管穩(wěn)定化是否可能能夠改變患者的臨床結(jié)果和病理結(jié)果,。”
在此之前，研究人員已證實這種藥物能夠阻止動物模型中的進一步神經(jīng)損傷和改善認知,。相關(guān)研究結(jié)果發(fā)表在Journal of Neuroscience期刊上,。(生物谷：Bioon.com)
本文編譯自Anti-tau drug improves cognition, decreases tau tangles in Alzheimer's disease models
doi: 10.1523/JNEUROSCI.3059-10.2010
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Epothilone D Improves Microtubule Density, Axonal Integrity, and Cognition in a Transgenic Mouse Model of Tauopathy
Kurt R. Brunden1,*, Bin Zhang1,*, Jenna Carroll1, Yuemang Yao1, Justin S. Potuzak2, Anne-Marie L. Hogan2, Michiyo Iba1, Michael J. James1, Sharon X. Xie3,4, Carlo Ballatore1,2, Amos B. Smith III2, Virginia M.-Y. Lee1, and John Q. Trojanowski
Neurons in the brains of those with Alzheimer's disease (AD) and many frontotemporal dementias (FTDs) contain neurofibrillary tangles comprised of hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs), and tau misfolding could lead to a loss of this function with consequent MT destabilization and neuronal dysfunction. Accordingly, a possible therapeutic strategy for AD and related “tauopathies” is treatment with a MT-stabilizing anti-cancer drug such as paclitaxel. However, paclitaxel and related taxanes have poor blood–brain barrier permeability and thus are unsuitable for diseases of the brain. We demonstrate here that the MT-stabilizing agent, epothilone D (EpoD), is brain-penetrant and we subsequently evaluated whether EpoD can compensate for tau loss-of-function in PS19 tau transgenic mice that develop forebrain tau inclusions, axonal degeneration and MT deficits. Treatment of 3-month-old male PS19 mice with low doses of EpoD once weekly for a 3 month period significantly improved CNS MT density and axonal integrity without inducing notable side-effects. Moreover, EpoD treatment reduced cognitive deficits that were observed in the PS19 mice. These results suggest that certain brain-penetrant MT-stabilizing agents might provide a viable therapeutic strategy for the treatment of AD and FTDs.
