Fetal nigral transplantation as a therapy for Parkinson's disease

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Abstract

Fetal nigral grafts have been demonstrated to survive, secrete dopamine, form synaptic connections with host neurons, and reverse behavioral disturbances in experimental models of parkinsonism. These findings suggest that fetal nigral grafting may be a useful therapy for patients with Parkinson's disease (PD). Recent preliminary clinical trials of transplantation in PD have shown increased striatal fluorodopa uptake (measured using positron emission tomography) and clinical benefit in some patients. An autopsy study of one patient who had received fetal nigral transplants demonstrated robust graft survival and striatal reinnervation, with no evidence of host-derived sprouting or immune rejection. The development of a successful clinical transplantation program depends on a careful consideration of the transplantation variables and the related long-term risks and benefits to the patients.

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      Within these studies, despite >80% of cells showing appropriate regional specification at the time of transplantation, the overall proportion of ventral midbrain dopaminergic (vmDA) neurons within grafts remains low. Likely underpinning this is the poor survival of vmDA progenitors/neuroblasts during cell preparation and immediately after implantation, as has been reported for fetal tissue (Olanow et al., 1996; Castilho et al., 2000), as well as the inclusion of a low proportion of highly proliferative non-vmDA progenitors within the donor cells (de Luzy et al., 2019; de Luzy et al., 2021). Several studies using vmDA fetal tissue have demonstrated that the maturity of donor cells at the time of engraftment can have a significant impact on graft composition and functional outcomes.

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    C.W. Olanow is at the Dept of Neurology, Mount Sinai School of Medicine, New York, NY, USA. J.H. Kordower is at the Dept of Neurological Sciences, Research Center for Brain Repair, Rush Presbyterian Medical Center, Chicago, IL, USA and T.B. Freeman is at the Dept of Neurosurgery and Pharmacology, University of South Florida, Tampa, FL, USA.

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