The history and status of dopamine cell therapies for Parkinson's disease

• Published in: BioEssays Vol. 46; no. 12; pp. e2400118 - n/a
• Main Authors: Barker, Roger A., Björklund, Anders, Parmar, Malin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2024; John Wiley and Sons Inc
• Subjects: Animals; Basic Medicine; brain; Cell therapy; Clinical Medicine; Clinical trials; Clinical Trials as Topic; Dopamine; Dopamine - metabolism; dopamine cell transplants; Dopamine receptors; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - transplantation; Drug development; Fetuses; G Force PD; History, 20th Century; History, 21st Century; human fetal ventral mesencephalic tissue; human pluripotent stem cell‐derived dopamine cells; Humans; Innervation; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mesencephalon; Movement disorders; Neostriatum; Neurodegenerative diseases; Neurologi; Neurology; Neurons; Neurosciences; Neurovetenskaper; Parkinson disease; Parkinson Disease - therapy; Parkinson's disease; Pluripotency; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - transplantation; Review; REVIEW ESSAY; Side effects; Stem Cell Transplantation - methods; Stem cells; Transplants; dopamine cell transplants; clinical trials; Parkinson's disease; human pluripotent stem cell‐derived dopamine cells; human fetal ventral mesencephalic tissue; G Force PD
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.202400118

Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell‐derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.