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    Neurofibrillary labels
    7.
    发明授权
    Neurofibrillary labels 有权
    神经原纤维标签

    公开(公告)号：US07335652B2

    公开(公告)日：2008-02-26

    申请号：US10665008

    申请日：2003-09-22

    申请人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    发明人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    IPC分类号： A61K31/54

    CPC分类号： C07D417/12 ,  C07D277/66 ,  C07D279/20 ,  G01N33/583 ,  G01N33/6896

    摘要： Disclosed are methods for determining the stage of neurofibrillary degeneration associated with a tauopathy in a subject believed to suffer from the disease, by (i) introducing into the subject a ligand capable of labeling aggregated paired helical filament (PHF) tau protein, (ii) determining the presence and/or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. The methods can be used for pre-mortem diagnosis and staging of tauopathies such as Alzheimer's Disease. Preferred ligands include sulphonated-benzothiazole-like compounds and diaminophenothiazines.

    摘要翻译： 公开了用于确定被认为患有疾病的受试者中与tau蛋白病相关的神经原纤维变性的阶段的方法，方法是（i）向受试者引入能够标记聚集的成对螺旋丝（PHF）tau蛋白的配体，（ii） 确定与受试者的脑内侧颞叶结合的细胞外聚集的PHF tau的配体的存在和/或量的量，（iii）将（ii）中确定的测定结果与受试者的神经原纤维变性程度相关联 。 这些方法可用于妊娠前诊断和分期的阿尔茨海默病等tau蛋白病。 优选的配体包括磺化苯并噻唑类化合物和二氨基吩噻嗪。

    Neurofibrillary labels
    9.
    发明申请
    Neurofibrillary labels 有权
    神经原纤维标签

    公开(公告)号：US20100285605A1

    公开(公告)日：2010-11-11

    申请号：US12662887

    申请日：2010-05-10

    申请人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    发明人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    IPC分类号： G01N33/566

    CPC分类号： C07D417/12 ,  C07D277/66 ,  C07D279/20 ,  G01N33/583 ,  G01N33/6896

    摘要： Disclosed are methods for determining the stage of neurofibrillary degeneration associated with a tauopathy in a subject believed to suffer from the disease, which methods comprise the steps of: (i) introducing into the subject a ligand capable of labelling aggregated paired helical filament (PHF) tau protein, (ii) determining the presence and\or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. The methods can be used for pre-mortem diagnosis and staging of tauopathies such as Alzheimer's Disease. Preferred ligands include sulphonated-benzothiazole-like compounds and diaminophenothiazines. Novel ligands (e.g. sulphonated-benzothiazole-like compounds) are also provided. The method may also include the use of “blocking ligands” to block competing binding sites. In other aspects the invention provides in vitro methods for identifying ligands capable of labeling aggregated PHF tau protein, the methods comprising the steps of: (i) providing a first agent suspected of being capable of labeling aggregated PHF tau protein, (ii) contacting (a) a tau protein or a derivative thereof containing the tau core fragment bound to a solid phase so as to expose a high affinity tau capture site, with (b) a liquid phase tau protein or derivative thereof capable of binding to the solid phase tau protein or derivative, and (c) said selected first agent and (d) a second agent known to be tau-tau binding inhibitor, (iii) selecting first agent which fully or partially relieves the inhibition of binding of the liquid phase tau protein or derivative of (b) to the solid phase tau protein or derivative of (a) by the inhibitor (d). Ligands may also be tested to confirm that they are not themselves inhibitors.

    摘要翻译： 公开了用于确定被认为患有疾病的受试者中与tau蛋白病相关的神经原纤维变性的阶段的方法，该方法包括以下步骤：（i）将能够标记聚集的成对螺旋丝（PHF）的配体引入受试者， tau蛋白，（ii）确定与受试者的脑内侧颞叶中细胞外聚集的PHF tau结合的配体的存在和/或量，（iii）将（ii）中确定的测定结果与 的神经原纤维变性。 这些方法可用于妊娠前诊断和分期的阿尔茨海默病等tau蛋白病。 优选的配体包括磺化苯并噻唑类化合物和二氨基吩噻嗪。 还提供了新的配体（例如磺化的苯并噻唑类化合物）。 该方法还可以包括使用“阻断配体”来阻止竞争结合位点。 在其它方面，本发明提供了用于鉴定能够标记聚集的PHF tau蛋白的配体的体外方法，所述方法包括以下步骤：（i）提供疑似能够标记聚集的PHF tau蛋白的第一药剂，（ii） a）包含与固相结合的tau核心片段的tau蛋白或其衍生物，以暴露高亲和力tau捕获位点，（b）能够结合固相tau的液相tau蛋白或其衍生物 蛋白质或衍生物，和（c）所述选择的第一试剂和（d）已知为tau-tau结合抑制剂的第二药剂，（iii）选择完全或部分缓解液相tau蛋白结合抑制的第一药剂，或 （b）衍生物与固相tau蛋白或（a）的抑制剂（d）的衍生物。 也可以测试配体以确认它们本身不是抑制剂。