公开(公告)号：US06787519B2

公开(公告)日：2004-09-07

申请号：US10033526

申请日：2001-11-02

申请人： Yadong Huang ,  Robert W. Mahley

发明人： Yadong Huang ,  Robert W. Mahley

IPC分类号： A61K3800

CPC分类号： C07K5/1008 ,  A01K2217/05 ,  A61K38/00 ,  C07K14/775

摘要： The present invention provides methods inhibiting formation of neurofibrillary tangles; and methods for treating disorders relating to apolipoprotein E (apoE) in a subject. The methods generally involve reducing the level of a carboxyl-terminal truncated form of apoE in a neuronal cell of a subject. The invention further provides isolated cells comprising a nucleic acid molecule encoding a carboxyl-terminal truncated form of apoE; and methods of screening compounds using the cells. The invention further provides compounds that inhibit an apoE cleavage enzyme, and that reduce the formation of neurofibrillary tangles in a neuronal cell. The invention further provides transgenic non-human animals that include as a transgene a nucleic acid that encodes a carboxyl-terminal truncated form of apoE; as well as methods of screening compounds using transgenic animals.

公开(公告)号：US20090136456A1

公开(公告)日：2009-05-28

申请号：US11961951

申请日：2007-12-20

申请人： Yadong Huang ,  Gang Li ,  Robert W. Mahley ,  Qin Xu

发明人： Yadong Huang ,  Gang Li ,  Robert W. Mahley ,  Qin Xu

IPC分类号： A61K35/12 ,  C12N5/00 ,  A61P25/28

CPC分类号： C12N5/0623 ,  A61K35/12 ,  C12N2501/115 ,  C12N2510/00

摘要： The present invention provides a selected population of neural cells, including neural stem cells, neural progenitor cells, neural precursor cells, and progeny thereof, which neural cells are selected for an apoE4− phenotype. In some embodiments, the neural cells are further selected for an apoE3+ phenotype. The selected population of neural cells is useful in treating various disorders, such as neurodegenerative disorders and demyelination diseases. The present invention further provides methods of treating neurodegenerative disorders and demyelinating diseases, generally involving administering a subject selected cell population.

摘要翻译： 本发明提供了选择的神经细胞群，包括神经干细胞，神经祖细胞，神经前体细胞及其后代，其选择了用于apoE4表型的神经细胞。 在一些实施方案中，进一步选择神经细胞用于apoE3 +表型。 所选择的神经细胞群可用于治疗各种疾病，例如神经变性疾病和脱髓鞘疾病。 本发明进一步提供治疗神经变性疾病和脱髓鞘疾病的方法，通常涉及给予受试者所选择的细胞群体。

公开(公告)号：US20090082271A1

公开(公告)日：2009-03-26

申请号：US12092550

申请日：2006-12-07

申请人： Robert W. Mahley ,  Yadong Huang

发明人： Robert W. Mahley ,  Yadong Huang

IPC分类号： A61K38/16 ,  A61P25/00

CPC分类号： A61K38/1709

摘要： The present invention provides isolated cells comprising a nucleic acid encoding a toxic form of apoE. The present invention further provides screening methods for identifying compounds that reduce apoE-induced impairment of mitochondrial integrity and/or function. The present invention further provides kits for use in carrying out a subject screening method. The present invention provides agents that reduce apoE-induced impairment of mitochondrial integrity and/or function; and use of such agents in the treatment of apoE-related disorders.

摘要翻译： 本发明提供了分离的细胞，其包含编码毒性形式的apoE的核酸。 本发明还提供用于鉴定减少apoE诱导的线粒体完整性和/或功能损伤的化合物的筛选方法。 本发明还提供了用于进行受试者筛选方法的试剂盒。 本发明提供减少apoE诱导的线粒体完整性和/或功能损伤的药剂; 以及这些药物在治疗apoE相关疾病中的用途。

公开(公告)号：US07964598B2

公开(公告)日：2011-06-21

申请号：US11244268

申请日：2005-10-04

申请人： Robert W. Mahley ,  Karl H. Weisgraber ,  Yadong Huang

发明人： Robert W. Mahley ,  Karl H. Weisgraber ,  Yadong Huang

IPC分类号： A61K31/535 ,  A61K31/42 ,  A61K31/38 ,  A01N43/76 ,  A01N43/12 ,  C07D498/00 ,  C07D487/00

CPC分类号： A61K31/185 ,  A61K31/381 ,  A61K31/423 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/655

摘要： The present invention provides compounds that inhibit apoE4 domain interaction; and compositions, including pharmaceutical compositions, comprising the compounds. The present invention provides methods of treating apoE4-related disorders. The methods generally involve administering to an individual in need thereof a therapeutically effective amount of an apoE4 domain interaction inhibitor.

摘要翻译： 本发明提供抑制apoE4结构域相互作用的化合物; 和包含该化合物的组合物，包括药物组合物。 本发明提供了治疗apoE4相关疾病的方法。 所述方法通常涉及向有需要的个体施用治疗有效量的apoE4结构域相互作用抑制剂。

公开(公告)号：US6046381A

公开(公告)日：2000-04-04

申请号：US70670

申请日：1998-04-30

申请人： Lennart Mucke ,  Jacob Raber ,  Manuel Buttini ,  Robert W. Mahley ,  Robert E. Pitas

发明人： Lennart Mucke ,  Jacob Raber ,  Manuel Buttini ,  Robert W. Mahley ,  Robert E. Pitas

IPC分类号： A01K67/027 ,  C07K14/775 ,  C12N5/10 ,  C12N15/09 ,  C12N15/85 ,  C12N5/00 ,  C12N15/00

CPC分类号： A01K67/0276 ,  A01K67/0278 ,  C07K14/775 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0306 ,  A01K2267/0318 ,  A01K2267/0356 ,  C12N2830/008

摘要： The present invention features non-human transgenic animal models for gene function, wherein the transgenic animal is characterized by having altered endogenous apolipoprotein E gene function and a transgene for an exogenous human apolipoprotein E isoform. The transgenic animals may be either homozygous or heterozygous for the transgene. The invention also features methods for using non-human transgenic animal models for the study of apolipoprotein E-mediated pathologies and the identification of compounds and therapies for such pathologies.

摘要翻译： 本发明的特征在于用于基因功能的非人转基因动物模型，其中所述转基因动物的特征在于具有改变的内源载脂蛋白E基因功能和外源人载脂蛋白E同种型的转基因。 转基因动物对于转基因可以是纯合的或杂合的。 本发明还具有使用非人转基因动物模型研究载脂蛋白E介导的病理学的方法以及鉴定这些病理学的化合物和疗法。

公开(公告)号：US07700304B2

公开(公告)日：2010-04-20

申请号：US10820618

申请日：2004-04-07

申请人： Yadong Huang ,  Robert W. Mahley

发明人： Yadong Huang ,  Robert W. Mahley

IPC分类号： G01N33/53

CPC分类号： C07K5/1008 ,  A01K2217/05 ,  A61K38/00 ,  C07K14/775

摘要： The present invention provides methods inhibiting formation of neurofibrillary tangles; and methods for treating disorders relating to apolipoprotein E (apoE) in a subject. The methods generally involve reducing the level of a carboxyl-terminal truncated form of apoE in a neuronal cell of a subject. The invention further provides isolated cells comprising a nucleic acid molecule encoding a carboxyl-terminal truncated form of apoE; and methods of screening compounds using the cells. The invention further provides compounds that inhibit an apoE cleavage enzyme, and that reduce the formation of neurofibrillary tangles in a neuronal cell. The invention further provides transgenic non-human animals that include as a transgene a nucleic acid that encodes a carboxyl-terminal truncated form of apoE; as well as methods of screening compounds using transgenic animals.

摘要翻译： 本发明提供抑制神经原纤维缠结形成的方法; 以及用于治疗受试者中与载脂蛋白E（apoE）相关的疾病的方法。 所述方法通常涉及降低受试者的神经元细胞中apoE的羧基末端截短形式的水平。 本发明还提供了包含编码apoE的羧基末端截短形式的核酸分子的分离的细胞; 以及使用细胞筛选化合物的方法。 本发明还提供抑制apoE切割酶并减少神经元细胞中神经原纤维缠结的形成的化合物。 本发明还提供了转基因非人动物，其包含编码apoE的羧基末端截短形式的核酸作为转基因; 以及使用转基因动物筛选化合物的方法。

公开(公告)号：US20120129782A1

公开(公告)日：2012-05-24

申请号：US13130003

申请日：2009-11-20

申请人： Yadong Huang ,  Qin Xu ,  Mei Xiu Steele ,  Robert W. Mahley ,  Karl H. Weisgraber ,  Stephen Barry Freedman

发明人： Yadong Huang ,  Qin Xu ,  Mei Xiu Steele ,  Robert W. Mahley ,  Karl H. Weisgraber ,  Stephen Barry Freedman

IPC分类号： A61K38/02 ,  C12Q1/37 ,  A61P25/28 ,  A61K31/713 ,  A61P29/00

CPC分类号： C12N15/1137 ,  A61K31/7088 ,  A61K45/06 ,  C07K14/775 ,  C12N2310/14 ,  C12N2310/531 ,  C12Y304/21092 ,  G01N33/92 ,  G01N2333/96433 ,  G01N2500/02 ,  G01N2800/2821 ,  A61K2300/00

摘要： The present invention provides methods for treating apoE-related disorders. The methods generally involve administering an effective amount of an agent that inhibits activity of an enzyme that cleaves apoE.

摘要翻译： 本发明提供了治疗apoE相关疾病的方法。 所述方法通常涉及施用有效量的抑制切割apoE的酶活性的试剂。