The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.

中文翻译：

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GDNF 和帕金森病：下一步在哪里？最近研讨会的摘要。


多年来，人们一直在利用生长因子修复大脑的概念来治疗各种神经退行性疾病，主要包括使用神经胶质细胞系衍生的神经营养因子（GDNF）治疗帕金森病（PD）。这种神经营养因子于 1993 年被发现，并被证明对促进某些神经元群（包括多巴胺能黑质纹状体通路）的存活和再生具有选择性作用。这些观察结果引发了针对 PD 患者的一系列临床试验，包括使用 GDNF 或相关生长因子神经营养因子 (NRTN) 的输注或基因递送。最初的研究（其中一些是开放标签的）表明，当药物被注射到壳核而不是脑室时，这种方法可能对 PD 有价值。在随后的双盲、安慰剂对照试验（最新报告于 2019 年）中，GDNF 治疗并未达到其主要终点。因此，GDNF（以及通过推断相关的 GDNF 家族神经营养因子）在未来 PD 治疗中是否有价值尚不确定。为了批判性地评估现有工作及其未来，举办了一次特别研讨会来讨论和辩论这个问题。本文是那次会议的总结，并提出了关于这种治疗方法是否有未来的建议，以及任何未来涉及 GDNF 和其他 GDNF 家族神经营养因子的 PD 试验在设计中应考虑的内容。