帕金森病的神经保护治疗王训.pptVIP

（一）PD目前使用神经保护剂–疗效 Definitions A neuroprotectant is generally defined as an agent that prevents neuronal death by inhibiting one or more of the pathophysiological steps in the processes that follow injury to the nervous system or ischemia due to occlusion of an artery or hypoxia due to any cause. This definition has now been extended to include protection against neurodegeneration and neurotoxins. The extended definition includes interventions that slow or halt the progression of neuronal degeneration. Neuroprotection may also be used for prevention of progression of a disease if it can be identified at a presymptomatic stage. The term neuroprotective, although an adjective, will be used as a noun in preference to neuroprotectant. 对PD分子病理生理学的认识提供了可能性停止或逆转病程的神经保护疗法。PD的神经变性过程中可能涉及，包括氧化应激，线粒体功能障碍和兴奋性毒性→细胞死亡，开始于症状前期。 PD神经保护治疗的另一个理由，是L-dopa和其代谢产物可能引起脂质过氧化、膜破裂、损伤线粒体呼吸链。 在PD的几种神经保护策略，虽然没有真正的神经保护药。“疾病修饰”药物(DMDs)不一定是采用临床评估神经保护疗法的症状改善，更相关的是停止或减缓日常生活中恶化；减缓衰退速度、改变疾病进展率，避免达到特定的临床状态，即改善病人长期预后。 抗PD药物中，具有抗氧化作用，如DA受体激动剂，作为神经保护剂在临床上使用，其他的临床试验中。 DA能药物可能中断的DA缺乏恶性循环，它导致丘脑底核脱抑制和Glu兴奋毒性，是DAR激动剂和选择性NMDA受体拮抗剂作用机制，外科干预也可以抑制丘脑核神经元放电（STN）。 （一）PD目前使用神经保护剂–疗效 TABLE 1. Failed clinical trials of disease-modifying therapies for PD from 2013 to 2015 Kalia LV, Kalia SK, Lang AE. Disease-modifying strategies for Parkinsons disease. Mov Disord. 2015. 30(11): 1442-50. Study Drug Mechanism of Action Trial Design Subjects Follow-up Period Primary Outcome Measure(s) Results Olanow et al., 20156 AAV2-Neuturin (injection into bilateral SNpc and putamen) Neuro trophic factor Multi-center, randomized, double-blind, sham surgery-controlled, phase 2 trial Advanced PD Subjects (n = 51) 15-24 months Change in UPDRS part 3 in practically defined “off”-state No statistically significant difference between treated and control PSG et al., 2014(QE3)8 Coenzyme Q10(1200 mg/d or 2400 mg/d) +vitamin E (1200 IU/d) Bioenergetic; Antioxidant Multi-center, randomiz