Characterisation and comparison of patient-derived cell therapy products in a pre-clinical Parkinson’s Disease model

Hills, Rachel 2023. Characterisation and comparison of patient-derived cell therapy products in a pre-clinical Parkinson’s Disease model. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

Current treatment options available to individuals with Parkinson’s disease largely aim to rebalance the affected dopamine output in the basal ganglia. These treatments are often associated with serious side effects, diminishing returns or invasive procedures. Cell replacement therapy has been proposed as a long-term, viable treatment strategy with several clinical trials completed or underway. Here we present data supporting an autologous cell replacement therapy aimed at reducing patient exposure to harmful immunosuppressants and supporting better engraftment of cells, due to the decreased immune response to a syngeneic transplant. A major barrier to autologous treatment lies in the development of a reproducible processing pipeline to generate reliable and efficacious cell therapy products from divergent cellular material individual donors. Cell lines were generated by Aspen Neuroscience Ltd, from multiple Parkinson’s donors, using their processing pipeline and quality control measures. We tested the engraftment and efficacy of 4 batches of cell therapy products from 4 different PD patients by intra-striatal transplantation into a preclinical rodent model of Parkinson’s disease. Assessment of motor function and behavioural observations were carried out at regular intervals over a 7 month graft maturation period . All patient cell therapy products were able to significantly reduce motor function deficits during this time by 63%, 100%, 95% and 73% for patient lines 1, 2, 3 and 4, respectively. Post mortem analysis of the transplants showed good engraftment and innervation of relevant brain areas with abundant mature dopamine neurons for all Parkinson’s disease donor derived cell therapy products.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	30 October 2024
Last Modified:	30 Oct 2024 17:02
URI:	https://orca.cardiff.ac.uk/id/eprint/173536

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