期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 49, 期 4, 页码 440-452出版社
WILEY
DOI: 10.1111/ejn.14102
关键词
animal models; CDNF; clinical trials; GDNF; neurotrophic factors; neurturin; Parkinson's disease; PDGF-BB
资金
- Knut and Alice Wallenberg Foundation
- Region Skane
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.
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