Trophic factors for Parkinson's disease: Where are we and where do we go from here?

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Date
2018-08-13
Authors
Gesine, Paul
Sullivan, Aideen M.
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Wiley
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Abstract
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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Keywords
Animal models , CDNF , Clinical trial , GDNF , Neurotrophic factors , Neurturin , Parkinson's disease , PDGF
Citation
Paul, G. and Sullivan, A. M. (2019) 'Trophic factors for Parkinson's disease: Where are we and where do we go from here?', European Journal of Neuroscience, 49(4), pp. 440-452. doi: 10.1111/ejn.14102
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© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Paul, G, Sullivan, AM. Trophic factors for Parkinson's disease: Where are we and where do we go from here?. Eur J Neurosci. 2019; 49: 440– 452, which has been published in final form at https://doi.org/10.1111/ejn.14102. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.