创新背景

在帕金森病（PD）患者中，大脑的某些部分多年来逐渐受损，导致运动症状，包括震颤、僵硬和运动迟缓（运动迟缓）。

这种恶化是由于大脑中一个叫做黑质的区域中产生多巴胺的神经元（神经细胞）的丢失造成的。反过来，这导致多巴胺的可用性降低，多巴胺作为神经递质（神经元释放的化学物质）向其他神经元发送信号，并在控制运动和平衡方面发挥作用。

创新过程

基因治疗的工作原理是通过灭活病毒载体（病毒）将基因导入特定细胞，为其提供改变命运所需的基因指令。
AXO-Lenti PD，也称为OXB-102，是下一代基因疗法，由国家健康研究所（NIHR）UCLH临床研究设施、皇后广场伦纳德·沃尔夫森实验神经学中心的UCL和UCLH研究人员首次进行测试。

该疗法由牛津生物医学和Axovant Sciences Ltd开发，用于治疗帕金森病，包含三个负责产生多巴胺的基因，通过慢病毒载体传递。

Axo-Lenti-PD将被注入大脑的一部分，称为纹状体，纹状体通常由黑质投射的细胞释放多巴胺。它是一种定义明确的结构，易于手术操作，使纹状体细胞的基因靶向成为一种可行的方法，对其他大脑区域的干扰最小。

轴突-慢斑帕金森病治疗帕金森病的治疗原理是通过多巴胺生物合成途径中三种关键酶的基因转移，为帕金森病患者的多巴胺缺失纹状体提供多巴胺替代。

增加多巴胺产生的基因可以帮助缓解帕金森氏症的症状，与传统药物治疗相比，潜在的副作用更少，只针对大脑中缺少多巴胺的区域。

据设想，轴突-慢斑帕金森病将有助于纹状体内多巴胺的持续供应，并在没有目前使口服药物的多巴胺替代治疗复杂化的致残副作用的情况下维持突触后多巴胺受体的刺激。

该试验将评估来自伦敦UCLH、伦敦国立神经外科医院（NHNN）、剑桥大学医院和巴黎亨利·蒙多尔医院的多达30名帕金森病患者。

试验A部分的患者将接受三种剂量的AXO-Lenti-PD中的一种，而B部分的患者则将接受A部分确定的最佳剂量或无治疗的模拟手术程序。患者将在手术后进行定期评估。

创新价值

这项研究将通过观察这种疗法对震颤、僵硬和运动迟缓等症状的影响，并观察它们是否改善，来研究这种疗法对帕金森病患者的潜在益处。

创新关键点

Axo-Lenti-PD将被注入大脑的一部分，称为纹状体，纹状体通常由黑质投射的细胞释放多巴胺。它是一种定义明确的结构，易于手术操作，使纹状体细胞的基因靶向成为一种可行的方法，对其他大脑区域的干扰最小。

Innovative gene therapy trials for Parkinson's disease

The working principle of gene therapy is to introduce genes into specific cells by inactivating viral vectors (viruses) to provide them with genetic instructions required to change their fate.
Axo lenti PD, also known as oxb-102, is a next-generation gene therapy, which was first tested by UCL and UCLH researchers at the UCLH clinical research facility of the National Institute of Health (NIHR) and the Leonard Wolfson experimental neurology center in Queen's Square.
The therapy was developed by Oxford biomedical and axovant Sciences Ltd for the treatment of Parkinson's disease and contains three genes responsible for dopamine production, which are delivered through lentiviral vectors.
Axo lenti PD will be injected into a part of the brain called the striatum, which normally releases dopamine from cells projecting from the substantia nigra. It is a well-defined structure and easy to operate, making gene targeting of striatal cells a feasible method with minimal interference to other brain regions.
The treatment principle of axonal slow spot Parkinson's disease is to provide dopamine replacement for the dopamine deficient striatum of Parkinson's disease patients through gene transfer of three key enzymes in the dopamine biosynthesis pathway.
Genes that increase dopamine production can help alleviate the symptoms of Parkinson's disease. Compared with traditional drug treatment, the potential side effects are less, and only target the regions of the brain that lack dopamine.
It is envisaged that axonal lenticular Parkinson's disease will contribute to the sustained supply of dopamine in the striatum and maintain the stimulation of postsynaptic dopamine receptors without the disabling side effects that currently complicate dopamine replacement therapy with oral drugs.
The trial will evaluate up to 30 patients with Parkinson's disease from UCLH in London, the national neurosurgery hospital in London (nhnn), the University Hospital in Cambridge and the Henri mundor hospital in Paris.
Patients in part a of the trial will receive one of the three doses of axo lenti PD, while patients in part B will receive the optimal dose determined in part a or the simulated surgical procedure without treatment. Patients will be regularly evaluated after surgery.