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Neurotrophic Factors in Parkinson’s Disease: Clinical Trials

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Regenerative Medicine and Brain Repair

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL,volume 75))

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Abstract

Introduction: Parkinson’s disease (PD) is characterized by the progressive loss of midbrain dopamine (DA) neurons that regulate voluntary movement and cognitive functions. Despite notable progress in the development of symptomatic therapy, the development of disease-modifying therapy for PD still holds big challenges. Neurotrophic factors (NTFs) are considered as potential regenerative therapy for PD because they can protect DA neurons and promote neuron survival both in vitro and in vivo. Although preclinical studies with the neurotrophic factors have proved to be efficient in animal PD models with mild lesions, the effect of NTFs on PD patients in clinical trials has been modest. In this review, we discuss the current state of NTFs therapies on PD treatment from preclinical and clinical studies, challenges with growth factors (GFs) therapy, and alternative approaches for further development of disease-modifying therapies. Methods: We formulated the questions and based on that, literature search was carried out using the PUBMED database. Further, we extracted the data, analyzed and summarized the findings. Results: GDNF family ligands GDNF and neurturin and CDNF/MANF neurotrophic factors are extensively studied in preclinical and clinical studies. In preclinical studies, these NTFs have demonstrated neurotrophic activities on DA neurons and have potential disease modifying properties in animal models of PD. However, the effect of NTFs in PD patients has been modest. Importantly, the results from clinical studies show beneficial effects of NTFs including improvements in motor symptoms and quality of life. Conclusion: NTFs still remains a potential candidate in the treatment of PD. However, development of GDNF based treatment has many difficulties related to effective delivery, poor diffusion and optimum dose. Regardless of the challenges, efforts to develop neurotrophic factors-based therapies should be continued towards clinical application in PD.

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Acknowledgements

We are grateful to Päivi Lindholm-Pulkkila and Vera Kovaleva for their valuable comments on the manuscript. This work was supported by Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Academy of Finland (grant number 1343299) and Enterprise Estonia. Figures 4.1 and 4.2 were created with BioRender.

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MS is a founder and shareholder at Herantis Pharma Plc. MS and AKM report unrelated research support from the GeneCode Ltd. and ArgoBio Studio.

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    Arun Kumar Mahato & Mart Saarma

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  1. Department of Anatomy, University of Otago, Dunedin, New Zealand

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    Bridget Martinez

  3. Professor Emeritus of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA

    Thomas A. Gennarelli

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Mahato, A.K., Saarma, M. (2024). Neurotrophic Factors in Parkinson’s Disease: Clinical Trials. In: Peplow, P.V., Martinez, B., Gennarelli, T.A. (eds) Regenerative Medicine and Brain Repair. Stem Cell Biology and Regenerative Medicine, vol 75. Springer, Cham. https://doi.org/10.1007/978-3-031-49744-5_4

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