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  • Review Article
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Challenges in the clinical advancement of cell therapies for Parkinson’s disease

Nature Biomedical Engineering volume 7, pages 370–386 (2023)Cite this article

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Abstract

Cell therapies as potential treatments for Parkinson’s disease first gained traction in the 1980s, owing to the clinical success of trials that used transplants of foetal midbrain dopaminergic tissue. However, the poor standardization of the tissue for grafting, and constraints on its availability and ethical use, have hindered this treatment strategy. Recent advances in stem-cell technologies and in the understanding of the development of dopaminergic neurons have enabled preclinical advancements of promising stem-cell therapies. To move these therapies to the clinic, appropriate levels of safety screening, as well as optimization of the cell products and the scalability of their manufacturing, will be required. In this Review, we discuss how challenges pertaining to cell sources, functional and safety testing, manufacturing and storage, and clinical-trial design are being addressed to advance the translational and clinical development of cell therapies for Parkinson’s disease.

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Fig. 1: Putative mechanism of action of parthenogenetic neural stem cells for the treatment of PD.
Fig. 2: Preclinical benchmarks of efficacy and safety required for stem-cell therapies for PD that are intended for use in clinical trials.
Fig. 3: Protocol for the differentiation of hESCs into dopaminergic progenitors.

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Acknowledgements

We thank S. Fazal for invaluable discussions on the use of stem cells for neurodegenerative diseases other than Parkinson’s disease, and V. Pisupati for help in understanding how graft survival is influenced by cell composition. The authors acknowledge funding from the Cambridge Trust, the Wellcome/MRC funded Cambridge Stem Cell Institute, the MRC funded UK RMP PSEC (MR/R015724/1) and the NIHR Cambridge Biomedical Research Centre (146281). The views expressed in this work are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

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  1. Wellcome and MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, UK

    Sophie Skidmore & Roger A. Barker

  2. John van Geest Centre for Brain Repair, Department of Clinical Neuroscience, For vie Site, Cambridge, UK

    Roger A. Barker

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R.A.B. and S.S. conceived, wrote and revised the manuscript.

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Correspondence to Roger A. Barker.

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R.A.B. offers consultancy advice around cell-based therapies for Parkinson’s disease to Living Cell Technologies, Fujifilm Cellular Dynamics Inc., BlueRock Therapeutics, Novo Nordisk, Cellino Biotech and Aspen Neuroscience. S.S. declares no competing interests.

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Skidmore, S., Barker, R.A. Challenges in the clinical advancement of cell therapies for Parkinson’s disease. Nat. Biomed. Eng 7, 370–386 (2023). https://doi.org/10.1038/s41551-022-00987-y

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