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    • 6. 发明申请
    • COMPOSITIONS AND METHODS FOR ENHANCING STRUCTURAL AND FUNCTIONAL NERVOUS SYSTEM REORGANIZATION AND RECOVERY
    • 用于增强结构和功能性神经系统重组和恢复的组合物和方法
    • WO2006023530A2
    • 2006-03-02
    • PCT/US2005/029214
    • 2005-08-16
    • MASSACHUSETTS INSTITUTE OF TECHNOLOGYORAY, SerkanSUR, Mriganka
    • ORAY, SerkanSUR, Mriganka
    • A61K38/44
    • A61K38/49A61K33/14A61K33/30A61K33/42A61K38/484A61K45/06A61L27/54A61L2300/254A61L2300/412A61K2300/00
    • The present invention provides methods and compositions for enhancing recovery in a subject suffering from damage to the nervous system. In particular, the invention includes a method for promoting recovery and/or reorganization in the nervous system of a subject in need of enhancement of recovery and/or reorganization of the nervous system as a result of ischemic, hemorrhagic, neoplastic, degenerative, or traumatic damage by focally administering a composition comprising a proteolysis-enhancing agent such as tissue plasminogen activator (tPA), plasmin, or a PAI inhibitor to the nervous system of the subject. In some embodiments an additional active agent is also administered. The composition can be delivered using a variety of techniques including injection, via infusion pump, from an implantable microchip, or using a polymeric delivery vehicle. The composition can be administered, for example, to one or more subdivisions or areas of the brain, the spinal cord, or to one or more nerves or nerve tracts innervating diverse regions of the body. The invention also includes a drug delivery device for implantation into the nervous system to promote nervous system reorganization and/or recovery following ischemic, hemorrhagic, neoplastic, traumatic or degenerative damage, the drug delivery device comprising a biocompatible polymer and a proteolysis-enhancing agent such as tissue plasminogen activator (tPA), plasmin, or a PAI inhibitor, wherein the proteolysis-enhancing agent is released from the polymer in an amount effective to promote structural reorganization of the nervous system. In some embodiments the biocompatible polymer is a hydrogel.
    • 本发明提供用于增强患有神经系统损伤的受试者的恢复的方法和组合物。 特别地,本发明包括促进需要增强神经系统的恢复和/或重组作为缺血性,出血性,肿瘤性,退行性或外伤性的结果的神经系统中的恢复和/或重组的方法。 通过向受试者的神经系统照射施用包含蛋白水解增强剂如组织纤溶酶原激活剂(tPA),纤溶酶或PAI抑制剂的组合物的损伤。 在一些实施方案中,还施用另外的活性剂。 组合物可以使用各种技术递送,包括注射,通过输注泵,可植入微芯片,或使用聚合物递送载体。 组合物可以例如施用于脑,脊髓的一个或多个细分或区域,或者一个或多个神经或神经束,其支配身体的不同区域。 本发明还包括用于植入神经系统以促进缺血性,出血性,肿瘤性,创伤性或退行性损伤后的神经系统重组和/或恢复的药物递送装置,药物递送装置包含生物相容性聚合物和蛋白水解增强剂,例如 作为组织纤溶酶原激活剂(tPA),纤溶酶或PAI抑制剂,其中蛋白水解增强剂以有效促进神经系统结构重组的量从聚合物中释放。 在一些实施方案中,生物相容性聚合物是水凝胶。
    • 7. 发明公开
    • IDENTIFYING AND MODULATING MOLECULAR PATHWAYS THAT MEDIATE NERVOUS SYSTEM PLASTICITY
    • 识别和调节介导神经系统可塑性的分子途径
    • EP2012815A2
    • 2009-01-14
    • EP07794351.2
    • 2007-04-12
    • Massachusetts Institute Of Technology
    • SUR, MrigankaTROPEA, DanielaKREIMAN, Gabriel
    • A61K38/21
    • A61K38/30A61K38/217A61K38/49A61K45/06A61K2300/00
    • The present invention provides methods for identifying genes and pathways involved in plasticity. The invention applies some of these methods to identify genes that are differentially regulated in at least a portion of the nervous system of an individual subjected to conditions known to result in altered nervous system plasticity, i.e., dark rearing (DR) or monocular deprivation (MD). The genes are targets for pharmacological agents that modify plasticity. The invention also identifies biological pathways that are enriched in genes that are differentially regulated under conditions known to result in altered nervous system plasticity. The present invention further provides methods and compositions for modifying plasticity in the nervous system of a subject. The invention includes a method for modifying plasticity in the nervous system of a subject comprising administering a plasticity-modifying agent to the subject, wherein the plasticity-enhancing agent modulates a gene or pathway that is differentially regulated in developmental conditions that alter nervous system plasticity (e.g., DR or MD). The methods and compositions may be administered to a subject suffering from damage to the nervous system or from a neuropsychiatric disorder in order to enhance recovery, reorganization, or function of the nervous system. The methods optionally include administering a proteolysis-enhancing agent to the subject.
    • 本发明提供了鉴定参与可塑性的基因和途径的方法。 本发明应用这些方法中的一些来鉴定在受到已知会导致神经系统可塑性改变的条件下(即黑暗抚养(DR)或单眼剥夺(MD))的个体的至少一部分神经系统中差异调节的基因 )。 这些基因是改变可塑性的药理学试剂的目标。 本发明还鉴定了在已知会导致神经系统可塑性改变的条件下差异调节的基因富集的生物途径。 本发明还提供了用于改变受试者神经系统可塑性的方法和组合物。 本发明包括用于改变受试者的神经系统中的可塑性的方法,其包括向受试者施用塑性改良剂,其中所述塑性增强剂调节在改变神经系统可塑性的发育条件中差异调节的基因或途径( 例如DR或MD)。 所述方法和组合物可以施用于患有神经系统损伤或神经精神障碍的受试者以增强神经系统的恢复,重组或功能。 该方法任选地包括向受试者施用蛋白水解增强剂。