Translational Neurology Group, Department of Clinical Science, Lund University, Lund, Sweden.
Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.
Eur J Neurosci. 2019 Feb;49(4):440-452. doi: 10.1111/ejn.14102. Epub 2018 Sep 9.
Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the development of a therapy that can slow or halt disease progression. Extensive preclinical research has provided evidence for the neurorestorative properties of several growth factors, yet only a few have been evaluated in clinical studies. Attempts to achieve neuroprotection by addressing cell-autonomous mechanisms and targeting dopaminergic neurons have been disappointing. Four different trophic factors have so far entered clinical trials in PD: glial cell line-derived growth factor, its close structural and functional analog neurturin, platelet-derived growth factor and cerebral dopaminergic neurotrophic factor. This article reviews the pre-clinical evidence for the neuroprotective and neurorestorative actions of these growth factors and discusses limitations of preclinical models, which may hamper successful translation to the clinic. We summarize the previous and ongoing clinical trials using growth factors in PD and emphasize the caveats in clinical trial design that may prevent the further development and registration of potentially neuroprotective and neurorestorative treatments for individuals suffering from PD.
或许帕金森病（PD）未满足的最重要临床需求是开发一种能够减缓或阻止疾病进展的疗法。广泛的临床前研究为多种生长因子的神经修复特性提供了证据，但只有少数几种在临床研究中进行了评估。通过解决细胞自主机制和靶向多巴胺能神经元来实现神经保护的尝试令人失望。到目前为止，已有四种不同的营养因子在 PD 临床试验中进行了尝试：胶质细胞系源性神经营养因子、其紧密的结构和功能类似物神经生长因子、血小板衍生生长因子和脑多巴胺能神经营养因子。本文综述了这些生长因子的神经保护和神经修复作用的临床前证据，并讨论了临床前模型的局限性，这些局限性可能会阻碍其成功转化为临床应用。我们总结了以前和正在进行的使用生长因子治疗 PD 的临床试验，并强调了临床试验设计中的注意事项，这些注意事项可能会阻止对患有 PD 的个体可能具有神经保护和神经修复作用的治疗方法的进一步开发和注册。
