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

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. However, to advance to the clinic, challenges in the appropriate levels of safety screening and optimization needed for the cell products as well as in the scalability of their manufacturing will need to be overcome. In this Review Article, we discuss how current challenges, pertaining to cell source, 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.

Clinical translation of pluripotent stem cell-based therapies: successes and challenges

“…Progressing hPSC-based cell therapies to clinic has been associated with three main challenges ( Armstrong et al, 2020 ; Barker et al, 2023 ; Skidmore and Barker, 2023 ). First, advancing differentiation protocols to a stage where authentic and functional cell types can be produced from hPSCs at high purity without the production of dangerous off-target cells has required years of research in studying and testing factors involved in tissue-specific cell type specification ( Karbassi et al, 2020 ; Kim et al, 2020 ; Wang et al, 2022 ).…”

Mesenchymal stem cell-derived exosomes as a new possible therapeutic strategy for Parkinson’s disease

“…However, there are still challenges with cell sources, the number of homing cells, functional and safety testing, manufacturing and storage, cell survival rate and immunomodulatory effects after implantation in vivo. While MSCs have demonstrated preclinical success in PD during clinical trials, some issues like the clinical-trial design, including cell dose, administration interval time and route of administration, are required to be improved [42,43].…”

Development and Evaluation of Novel Apomorphine and Quetiapine Combinational Formulation for Parkinson’s Disease in Rat: New Era (Possibilities) for Pre – Clinical Protocol Concept Review

“…The pharmacokinetics of the drugs is essential for optimizing dosing regimens and minimizing adverse effects. Although the individual pharmacokinetics of apomorphine and quetiapine has been previously studied, the pharmacokinetics of the combination formulation has not been adequately evaluated [32,33]. Huang and colleagues have provided valuable insights into the pharmacokinetics of the apomorphine and quetiapine combination formulation in rats, suggesting that it may have superior properties to the individual drugs [34].…”