Evans Jonathan R, Barker Roger A
University of Cambridge, Cambridge Centre for Brain Repair, Department of Clinical Neuroscience, UK.
Expert Opin Ther Targets. 2008 Apr;12(4):437-47. doi: 10.1517/14728222.12.4.437.
The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered.
In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data.
Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised.
NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.
寻找可能改变帕金森病（PD）病程的治疗药物的研究正在进行中。一个特别受关注的领域涉及神经营养因子（NTFs），其中胶质细胞系源性神经营养因子（GDNF）家族的神经营养因子显示出最大的前景。这些疗法的安全性和有效性最近受到了质疑。此外，许多与这类疗法相关的关键问题，如最佳给药方法、治疗时机以及最可能受益患者的选择，仍未得到解答。
在本综述中，我们试图评估神经营养因子在治疗帕金森病中的治疗潜力。在对相关临床试验数据进行批判性评估之前，我们先评估了体外和体内研究提供的证据。
通过对截至2007年10月发表的文章进行PubMed检索来确定相关文献。检索词包括：“帕金森病”、“神经营养因子”、“BDNF”（脑源性神经营养因子）、“GDNF”和“Neurturin”。对原始文章进行了综述，并对这些文章的相关引用也进行了评估。
神经营养因子疗法在治疗帕金森病黑质纹状体功能障碍方面具有潜力，但在这种方法能够被广泛采用之前，需要解决许多方法学和安全性问题。此外，现在人们认识到帕金森病不仅仅是一种单纯的运动障碍，而且神经元损失不仅局限于多巴胺能黑质纹状体系统。帕金森病的非运动症状不太可能从仅针对黑质纹状体系统的疗法中获益，这一点必须影响我们对神经营养因子可能提供的最大可实现益处的思考。
