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1. 发明申请

WO2006024947A3 METHODS AND MATERIALS RELATING TO ENHANCED PRODUCTION OF DOPAMINE NEURONS 审中-公开
标题翻译：有关增强多巴胺神经元生成的方法和材料
公开(公告)号：WO2006024947A3
公开(公告)日：2006-08-10
申请号：PCT/IB2005002803
申请日：2005-09-02
申请人： NEURO THERAPEUTICS AB , ARENAS CASES ERNESTO A , CASTELO BRANCO GONCALO , RAWAL NINA
发明人： ARENAS CASES ERNESTO A , CASTELO BRANCO GONCALO , RAWAL NINA
IPC分类号： A61K31/404 , A61K31/55 , A61P25/16 , C12N5/0793 , C12N5/10
CPC分类号： G01N33/5023 , A61K31/404 , A61K31/55 , A61K38/1808 , A61K38/1825 , A61K38/2093 , A61K45/06 , C12N5/0619 , C12N2501/70 , C12N2501/999 , G01N33/5058 , G01N33/5073 , G01N2800/2835 , A61K2300/00
摘要： Induction of neuronal fate in neural stem cells or neural progenitor or precursor cells, or other stem cells, and enhancement of induction of a specific neuronal phenotype, and particularly to induction and enhancement of induction of a midbrain dopaminergic neuronal phenotype. Expressing a nuclear receptor of the Nurr1 subfamily above basal levels within the cell, and regulating GSK-3ß inhibition within the cell other than by means of a ligand for a Frizzled receptor.
摘要翻译：诱导神经干细胞或神经祖细胞或前体细胞或其他干细胞中的神经元命运，以及增强特定神经元表型的诱导，特别是诱导和增强诱导中脑多巴胺能神经元表型。在细胞内表达Nurr1亚家族的核受体超过基础水平，并且除了通过用于卷曲蛋白受体的配体调节细胞内的GSK-3β抑制外。

2. 发明申请

WO2008071960A3 METHODS OF INCREASING NEUROGENESIS 审中-公开
标题翻译：增加神经发生的方法
公开(公告)号：WO2008071960A3
公开(公告)日：2009-05-28
申请号：PCT/GB2007004765
申请日：2007-12-12
申请人： NEURO THERAPEUTICS AB , ARENAS ERNEST , HALL ANITA , SACCHETTI PAOLA , SOUSA KYLE , LISTE ISABEL
发明人： ARENAS ERNEST , HALL ANITA , SACCHETTI PAOLA , SOUSA KYLE , LISTE ISABEL
IPC分类号： A61K31/00 , A61K31/56 , A61K31/575 , A61P25/16 , A61P25/28 , C07J9/00 , C07J41/00
CPC分类号： A61K31/00 , A61K31/56 , A61K31/575 , C07J9/00 , C07J9/005 , C07J41/0055
摘要： This invention relates to the promotion of neurogenesis in progenitor or precursor cells by modulation of the amount of liver X receptor (LXR) signalling in said cells. Increased LXR signalling is shown herein to promote neurogenesis and reduced LXR signalling is shown to promote gliogenesis. Methods of the invention may be useful, for example, in cell replacement therapies for treating conditions characterised by neuronal loss, damage or dysfunction, such as Parkinson's disease, Huntington's disease, stroke and motor neuron disease, and for studying signalling events in neurons and the effects of drugs on neurons in vitro.
摘要翻译：本发明涉及通过调节所述细胞中的肝X受体（LXR）信号量来促进祖细胞或前体细胞中的神经发生。本文显示增加的LXR信号传导以促进神经发生，并且显示减少的LXR信号传导以促进神经发生。本发明的方法可用于例如用于治疗以神经元丧失，损伤或功能障碍为特征的疾病的细胞替代疗法，例如帕金森病，亨廷顿舞蹈病，中风和运动神经元疾病，以及用于研究神经元中的信号事件和药物对体外神经元的影响。

3. 发明申请

WO2007119180A3 SURVIVAL AND DEVELOPMENT OF NEURAL CELLS 审中-公开
标题翻译：神经细胞的生存和发育
公开(公告)号：WO2007119180A3
公开(公告)日：2008-06-05
申请号：PCT/IB2007002345
申请日：2007-04-05
申请人： NEURO THERAPEUTICS AB , ARENAS ERNESTO , MIRA HELENA , EDMAN LINDA , SOUSA KYLE
发明人： ARENAS ERNESTO , MIRA HELENA , EDMAN LINDA , SOUSA KYLE
IPC分类号： A61K35/30 , A61P25/02 , C12N5/0793
CPC分类号： C12N5/0619 , C12N2501/21 , C12N2501/58 , G01N33/5014 , G01N33/5023 , G01N33/6896 , G01N2500/10
摘要： Promoting survival, maturation and/or differentiation of a stem or neural cell, by means of modulating activity of a protein encoded by a Nurr1 up-regulated gene or a Nurr1 down-regulated gene in the cell.
摘要翻译：通过调节细胞中由Nurr1上调基因或Nurr1下调基因编码的蛋白质的活性，促进茎或神经细胞的存活，成熟和/或分化。

4. 发明申请

WO2006061717A2 MATERIALS AND METHODS RELATED TO DICKKOPFS AND NEUROGENESIS 审中-公开
标题翻译：与DICKKOPFS和神经发生相关的材料和方法
公开(公告)号：WO2006061717A2
公开(公告)日：2006-06-15
申请号：PCT/IB2005/003996
申请日：2005-12-09
申请人： NEURO THERAPEUTICS AB , ARENAS, Ernesto , CASTELO BRANCO, Goncalo , SOUSA, Kyle
发明人： ARENAS, Ernesto , CASTELO BRANCO, Goncalo , SOUSA, Kyle
IPC分类号： C12N5/079 , C12N5/0793
CPC分类号： A61K38/1709 , C12N5/0619 , C12N5/0622 , C12N2502/02 , C12N2506/02 , G01N33/5058 , G01N33/5073 , G01N2800/2835
摘要： Materials and Methods related to Dickkopfs and Neurogenesis Abstract Methods for promoting dopaminergic neuronal development and producing neural cells having a dopaminergic phenotype. Dopaminergic neural cells may be used for treating individuals having a neurodegenerative disease such as Parkinson's disease. Dopaminergic cells may be implanted into the brain of the individual, and/or dopaminergic neural development may be induced or enhanced in the brain of the individual. Methods comprise treating the cell with a Dkk ligand, such as any one of Dkk1 to Dkk4 or a fragment thereof comprising a cysteine rich domain, or a Dkk receptor such as LRP5 or LRP6, thereby producing or enhancing proliferation, self-renewal, survival and/or dopaminergic induction, differentiation, survival or acquisition of a neuronal dopaminergic phenotype. The cell may be co-cultured with astrocytes or glial cells and may be contacted with an FGF growth factor. Dopaminergic neurons may also be useful in drug/toxicology testing and for target development or drug discovery.
摘要翻译：与Dickkopfs和神经发生有关的材料和方法Abstract Abstract促进多巴胺能神经元发育和产生具有多巴胺能表型的神经细胞的方法。多巴胺能神经细胞可用于治疗患有神经变性疾病如帕金森病的个体。可以将多巴胺能细胞植入个体的脑中，和/或多巴胺能神经发育可以在个体的大脑中被诱导或增强。方法包括用Dkk配体，例如Dkk1至Dkk4中的任一种或其包含富含半胱氨酸的结构域或Dkk受体如LRP5或LRP6的片段处理细胞，从而产生或增强增殖，自我更新，存活和 /或多巴胺能诱导，分化，存活或获得神经元多巴胺能表型。细胞可与星形胶质细胞或神经胶质细胞共培养，并可与FGF生长因子接触。多巴胺能神经元也可用于药物/毒理学测试和目标开发或药物发现。

5. 发明申请

WO2006024947A2 METHODS AND MATERIALS RELATING TO ENHANCED PRODUCTION OF DOPAMINE NEURONS 审中-公开
标题翻译：关于增强多巴胺神经元生产的方法和材料
公开(公告)号：WO2006024947A2
公开(公告)日：2006-03-09
申请号：PCT/IB2005/002803
申请日：2005-09-02
申请人： NEURO THERAPEUTICS AB , ARENAS CASES, Ernesto, A , CASTELO BRANCO, Gonçalo , RAWAL, Nina
发明人： ARENAS CASES, Ernesto, A , CASTELO BRANCO, Gonçalo , RAWAL, Nina
IPC分类号： C12N5/06 , C12N5/08 , C12N5/10 , A61K31/404 , A61K31/55 , A61P25/16
CPC分类号： G01N33/5023 , A61K31/404 , A61K31/55 , A61K38/1808 , A61K38/1825 , A61K38/2093 , A61K45/06 , C12N5/0619 , C12N2501/70 , C12N2501/999 , G01N33/5058 , G01N33/5073 , G01N2800/2835 , A61K2300/00
摘要： Induction of neuronal fate in neural stem cells or neural progenitor or precursor cells, or other stem cells, and enhancement of induction of a specific neuronal phenotype, and particularly to induction and enhancement of induction of a midbrain dopaminergic neuronal phenotype. Expressing a nuclear receptor of the Nurr1 subfamily above basal levels within the cell, and regulating GSK-3ß inhibition within the cell other than by means of a ligand for a Frizzled receptor.
摘要翻译：诱导神经干细胞或神经祖细胞或其他干细胞中的神经元命运，以及增强特异性神经元表型的诱导，特别是诱导和增强中脑多巴胺能神经元表型的诱导。将Nurr1亚家族的核受体表达在细胞内的基础水平以上，并且通过用于卷曲受体的配体调节细胞内的GSK-3β抑制。

6. 发明申请

WO2004029229A3 METHODS FOR PROMOTING DOPAMINERGIC NEURONAL DEVELOPMENT BY USING NG4A-SUBFAMILY AND WNT-LIGANDS 审中-公开
标题翻译：通过使用NG4A-SUBFAMILY和WNT-LIGANDS促进多巴胺神经发育的方法
公开(公告)号：WO2004029229A3
公开(公告)日：2004-07-22
申请号：PCT/IB0304598
申请日：2003-09-24
申请人： NEURO THERAPEUTICS AB , ARENAS ERNESTO , WAGNER JOSEPH , BRANCO GONCALO CASTELO , SOUSA KYLE
发明人： ARENAS ERNESTO , WAGNER JOSEPH , BRANCO GONCALO CASTELO , SOUSA KYLE
IPC分类号： A61K38/18 , A61K48/00 , A61P25/16 , C12N5/0793 , C12N15/06 , G01N33/68 , G01N33/94 , C12N15/00 , A61K35/00 , C12N15/09 , C12Q1/68 , G01N33/50
CPC分类号： G01N33/9413 , A61K31/11 , A61K31/203 , A61K31/357 , A61K35/30 , A61K38/1783 , A61K38/18 , A61K38/1825 , A61K48/00 , C12N5/0619 , C12N2501/38 , C12N2501/415 , C12N2502/08 , C12N2502/99 , G01N33/6872 , G01N33/6896 , G01N2800/2835 , A61K2300/00 , A61K38/00
摘要： Methods for promoting dopaminergic neuronal development and producing neural cells having a dopaminergic phenotype. Dopaminergic neural cells may be used for treating individuals having a neurodegenerative disease such as Parkinson's disease. Dopaminergic cells may be implanted into the brain of the individual, and/or dopaminergic neural development may be induced or enhanced in the brain of the individual. Methods comprise expressing a nuclear receptor of the NG4A subfamily, e.g. Nurr1, above basal levels within the cell and treating the cell with a Wnt ligand, thereby producing or enhancing proliferation, self-renewal, survival and/or dopaminergic induction, differentiation, survival or acquisition of a neuronal dopaminergic phenotype. The cell may be co-cultured with astrocytes or glial cells and may be contacted with an FGF growth factor.
摘要翻译：促进多巴胺能神经元发育和产生具有多巴胺能表型的神经细胞的方法。多巴胺能神经细胞可用于治疗患有神经变性疾病如帕金森病的个体。可以将多巴胺能细胞植入个体的脑中，和/或多巴胺能神经发育可以在个体的大脑中被诱导或增强。方法包括表达NG4A亚家族的核受体。 Nurr1，高于细胞内的基础水平，用Wnt配体处理细胞，从而产生或增强神经元多巴胺能表型的增殖，自我更新，存活和/或多巴胺能诱导，分化，存活或获得。细胞可与星形胶质细胞或神经胶质细胞共培养，并可与FGF生长因子接触。

7. 发明申请

WO2008071960A2 METHODS OF INCREASING NEUROGENESIS 审中-公开
标题翻译：增加神经发生的方法
公开(公告)号：WO2008071960A2
公开(公告)日：2008-06-19
申请号：PCT/GB2007/004765
申请日：2007-12-12
申请人： NEURO THERAPEUTICS AB , ARENAS, Ernest , HALL, Anita , SACCHETTI, Paola , SOUSA, Kyle , LISTE, Isabel
发明人： ARENAS, Ernest , HALL, Anita , SACCHETTI, Paola , SOUSA, Kyle , LISTE, Isabel
IPC分类号： A61K31/00 , A61K31/56 , A61K31/575 , C07J9/00 , C07J41/00 , A61P25/16 , A61P25/28
CPC分类号： A61K31/00 , A61K31/56 , A61K31/575 , C07J9/00 , C07J9/005 , C07J41/0055
摘要： This invention relates to the promotion of neurogenesis in progenitor or precursor cells by modulation of the amount of liver X receptor (LXR) signalling in said cells. Increased LXR signalling is shown herein to promote neurogenesis and reduced LXR signalling is shown to promote gliogenesis. Methods of the invention may be useful, for example, in cell replacement therapies for treating conditions characterised by neuronal loss, damage or dysfunction, such as Parkinson's disease, Huntington's disease, stroke and motor neuron disease, and for studying signalling events in neurons and the effects of drugs on neurons in vitro.
摘要翻译：本发明涉及通过调节所述细胞中的肝X受体（LXR）信号量来促进祖细胞或前体细胞中的神经发生。本文显示增加的LXR信号传导以促进神经发生，并且显示减少的LXR信号传导以促进神经发生。本发明的方法可用于例如用于治疗以神经元丧失，损伤或功能障碍为特征的疾病的细胞替代疗法，例如帕金森病，亨廷顿舞蹈病，中风和运动神经元疾病，以及用于研究神经元中的信号事件和药物对体外神经元的影响。

8. 发明申请

WO2007119180A2 SURVIVAL AND DEVELOPMENT OF NEURAL CELLS 审中-公开
标题翻译：神经细胞的生存和发育
公开(公告)号：WO2007119180A2
公开(公告)日：2007-10-25
申请号：PCT/IB2007/002345
申请日：2007-04-05
申请人： NEURO THERAPEUTICS AB , ARENAS, Ernesto , MIRA, Helena , EDMAN, Linda , SOUSA, Kyle
发明人： ARENAS, Ernesto , MIRA, Helena , EDMAN, Linda , SOUSA, Kyle
IPC分类号： C12N5/0793
CPC分类号： C12N5/0619 , C12N2501/21 , C12N2501/58 , G01N33/5014 , G01N33/5023 , G01N33/6896 , G01N2500/10
摘要： Promoting survival, maturation and/or differentiation of a stem or neural cell, by means of modulating activity of a protein encoded by a Nurr1 up-regulated gene or a Nurr1 down-regulated gene in the cell.
摘要翻译：通过调节细胞中由Nurr1上调基因或Nurr1下调基因编码的蛋白质的活性，促进茎或神经细胞的存活，成熟和/或分化。

9. 发明申请

WO2006061717A3 MATERIALS AND METHODS RELATED TO DICKKOPFS (DKK) AND NEUROGENESIS 审中-公开
标题翻译：材料与DICKKOPFS（DKK）和神经发生相关的方法
公开(公告)号：WO2006061717A3
公开(公告)日：2007-07-05
申请号：PCT/IB2005003996
申请日：2005-12-09
申请人： NEURO THERAPEUTICS AB , ARENAS ERNESTO , CASTELO BRANCO GONCALO , SOUSA KYLE
发明人： ARENAS ERNESTO , CASTELO BRANCO GONCALO , SOUSA KYLE
IPC分类号： A61K38/00 , C12N5/079 , C12N5/0793
CPC分类号： A61K38/1709 , C12N5/0619 , C12N5/0622 , C12N2502/02 , C12N2506/02 , G01N33/5058 , G01N33/5073 , G01N2800/2835
摘要： Materials and Methods related to Dickkopfs and Neurogenesis Abstract Methods for promoting dopaminergic neuronal development and producing neural cells having a dopaminergic phenotype. Dopaminergic neural cells may be used for treating individuals having a neurodegenerative disease such as Parkinson's disease. Dopaminergic cells may be implanted into the brain of the individual, and/or dopaminergic neural development may be induced or enhanced in the brain of the individual. Methods comprise treating the cell with a Dkk ligand, such as any one of Dkk1 to Dkk4 or a fragment thereof comprising a cysteine rich domain, or a Dkk receptor such as LRP5 or LRP6, thereby producing or enhancing proliferation, self-renewal, survival and/or dopaminergic induction, differentiation, survival or acquisition of a neuronal dopaminergic phenotype. The cell may be co-cultured with astrocytes or glial cells and may be contacted with an FGF growth factor. Dopaminergic neurons may also be useful in drug/toxicology testing and for target development or drug discovery.
摘要翻译：与Dickkopfs和神经发生有关的材料和方法Abstract Abstract促进多巴胺能神经元发育和产生具有多巴胺能表型的神经细胞的方法。多巴胺能神经细胞可用于治疗患有神经变性疾病如帕金森病的个体。可以将多巴胺能细胞植入个体的脑中，和/或多巴胺能神经发育可以在个体的大脑中被诱导或增强。方法包括用Dkk配体，例如Dkk1至Dkk4中的任一种或其包含富含半胱氨酸的结构域或Dkk受体如LRP5或LRP6的片段处理细胞，从而产生或增强增殖，自我更新，存活和 /或多巴胺能诱导，分化，存活或获得神经元多巴胺能表型。细胞可与星形胶质细胞或神经胶质细胞共培养，并可与FGF生长因子接触。多巴胺能神经元也可用于药物/毒理学测试和目标开发或药物发现。

10. 发明申请

WO2004029229A2 METHOD AND MATERIALS RELATING TO NEUROGENESIS 审中-公开
标题翻译：与神经发生相关的方法和材料
公开(公告)号：WO2004029229A2
公开(公告)日：2004-04-08
申请号：PCT/IB2003/004598
申请日：2003-09-24
申请人： NEURO THERAPEUTICS AB , ARENAS, Ernesto , WAGNER, Joseph , BRANCO, Goncalo, Castelo , SOUSA, Kyle
发明人： ARENAS, Ernesto , WAGNER, Joseph , BRANCO, Goncalo, Castelo , SOUSA, Kyle
IPC分类号： C12N5/00
CPC分类号： G01N33/9413 , A61K31/11 , A61K31/203 , A61K31/357 , A61K35/30 , A61K38/1783 , A61K38/18 , A61K38/1825 , A61K48/00 , C12N5/0619 , C12N2501/38 , C12N2501/415 , C12N2502/08 , C12N2502/99 , G01N33/6872 , G01N33/6896 , G01N2800/2835 , A61K2300/00 , A61K38/00
摘要： Methods for promoting dopaminergic neuronal development and producing neural cells having a dopaminergic phenotype. Dopaminergic neural cells may be used for treating individuals having a neurodegenerative disease such as Parkinson's disease. Dopaminergic cells may be implanted into the brain of the individual, and/or dopaminergic neural development may be induced or enhanced in the brain of the individual. Methods comprise expressing a nuclear receptor of the NG4A subfamily, e.g. Nurr1, above basal levels within the cell and treating the cell with a Wnt ligand, thereby producing or enhancing proliferation, self-renewal, survival and/or dopaminergic induction, differentiation, survival or acquisition of a neuronal dopaminergic phenotype. The cell may be co-cultured with astrocytes or glial cells and may be contacted with an FGF growth factor.
摘要翻译：促进多巴胺能神经元发育和产生具有多巴胺能表型的神经细胞的方法。多巴胺能神经细胞可用于治疗患有神经变性疾病如帕金森病的个体。可以将多巴胺能细胞植入个体的脑中，和/或多巴胺能神经发育可以在个体的大脑中被诱导或增强。方法包括表达NG4A亚家族的核受体。 Nurr1，高于细胞内的基础水平，用Wnt配体处理细胞，从而产生或增强神经元多巴胺能表型的增殖，自我更新，存活和/或多巴胺能诱导，分化，存活或获得。细胞可与星形胶质细胞或神经胶质细胞共培养，并可与FGF生长因子接触。

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