公开(公告)号：EP2972329A2

公开(公告)日：2016-01-20

申请号：EP14730243.4

申请日：2014-03-17

申请人： Kinemed, Inc. ,  Hellerstein, Marc ,  Fanara, Patrizia

发明人： HELLERSTEIN, Marc ,  FANARA, Patrizia

IPC分类号： G01N33/50 ,  G01N33/68

CPC分类号： G01N33/58 ,  G01N33/5023 ,  G01N33/5058 ,  G01N33/5088 ,  G01N33/6848 ,  G01N33/6896

摘要： The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules and microtubule-mediated axonal transport of cargo molecules in neurons), with or without dementia, and in dementia; methods for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease, with or without dementia, and in dementia; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can improve MT-mediated transport of cargo molecules along and through axons; the discovery that such modulation of altered microtubule dynamics and improvement in MT -transport of molecules along axons can provide marked neuroprotective therapy for living subjects with motoneuron diseases, including delay in symptoms and prolongation of survival; and the discovery that monitoring of microtubule-mediated axonal transport of cargo molecules in response to therapeutic interventions in subjects with motoneuron diseases, with or without dementia,and in dementia allows diagnostic monitoring, to optimize therapeutic regimens and treatment strategies in individual subjects or in drug trials.

摘要翻译： 本文公开的发明描述了运动神经元疾病（改变神经元中的货物分子的微管和微管介导的轴突运输的动力学），伴或不伴痴呆以及痴呆的新型治疗靶点; 用于测定具有确定的，初期的或潜在的运动神经元疾病，伴或不伴痴呆以及痴呆的受试者中该治疗靶活性状态的方法; 发现调节运动神经元疾病活体患者的神经元微管动力学的药物; 发现单独或联合给予这些药物可以改善MT-介导的货物分子沿着和穿过轴突的运输; 发现这种对微管动力学改变的调节和MT-轴突分子运输的改善可以为运动神经元疾病的活体患者提供显着的神经保护性治疗，包括延缓症状和延长生存期; 以及在运动神经元疾病患者，伴或不伴痴呆患者以及痴呆患者进行治疗性干预措施时，监测微管介导的货物分子的轴突转运可以进行诊断监测，以优化个体受试者或药物治疗方案和治疗策略 试验。