帕金森病(PD)是一种慢性神经系统疾病,由运动迟缓等症状的特征性组合确定,静止性震颤,刚性,和姿势不稳定。它是仅次于阿尔茨海默病的第二常见的神经退行性疾病,其特征是大脑中产生多巴胺的神经元逐渐丧失。目前,PD的可用治疗是有症状的,不能预防疾病病理。人们对开发可以减少疾病进展并改善患者生活质量的疾病改善疗法越来越感兴趣。正在评估的有希望的治疗方法之一是利用病毒载体的基因治疗,腺相关病毒(AAV),将感兴趣的转基因递送到中枢神经系统(CNS)中。PD的小动物和非人灵长类动物模型的临床前研究显示,利用表达神经胶质细胞系源性神经营养因子(GDNF)的基因治疗,脑多巴胺神经营养因子(CDNF),芳香族L-氨基酸脱羧酶(AADC),和谷氨酸脱羧酶(GAD)。本研究全面综述了上述基因治疗在PD治疗临床试验各个阶段的现状。我们强调了基因治疗方法的基本原理以及临床前和非人灵长类动物研究的发现,评估治疗效果,剂量安全,和耐受性。与异质性神经退行性疾病的基因治疗相关的挑战,比如PD,也有描述。总之,该综述确定了临床试验中正在进行的有希望的基因治疗方法,并为PD患者提供了希望.
Parkinson\'s disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer\'s disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients\' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.