Stem cell (dopamine cell replacement) therapies for Parkinson’s
Although the underlying cause of Parkinson’s is unknown, scientists do know that Parkinson’s results from the impairment and loss of dopamine producing cells in an area of the brain called the substantia nigra. It stands to reason therefore that replacement of those cells is a viable and potentially potent treatment method.
Although it is acknowledged that Parkinson’s symptoms extend to other areas of the body such as the gut, by replacing the lost dopamine neurons in the brain we can at least address the motor features of the condition; reducing dependence on medication and improving quality of life.
The most promising cell replacement therapy being developed for Parkinson’s at present is dopamine cell replacement transplantation. This approach involves injecting new dopamine producing neurons into the part of the brain to replace the dead or dying neurons.
Cell transplantation therapies date back to the late 80’s and 90’s, when a number of clinical trials for Parkinson’s were conducted. The procedures in those trials varied and this resulted in mixed results. But the science has progressed in this field enormously over time and we now have a much better understanding of what kind of cells to use, how to develop and nurture the cells, how to implant them, and for whom this therapy would be best suited.
Cure Parkinson’s is currently part funding a clinical trial focused on cell transplantation. The TRANSEURO study, led by Prof. Roger Barker (University of Cambridge), is investigating the transplantation of human foetal-derived dopamine neurons and aims to address issues of consistent efficacy from the earlier studies. A total of 13 people (in the UK and Sweden) have received the transplantations in this study and they will be followed up long-term. This study is also developing the protocols that will be used for the future of dopamine cell replacement therapy using human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs).
In addition to the TRANSEURO study, there are a number of stem cell-based clinical trials of cell transplantation getting underway around the world. Professors Roger Barker, Malin Parmar, Claire Henchcliffe and Jun Takahashi are part of an international consortium of labs working on cell transplantation in Parkinson’s under the name of GForce-PD, Cure Parkinson’s hosted the sixth G-Force PD meeting in Cambridge in April 2019. Each lab in the GForce-PD group aims to bring dopamine replacement cell replacement therapy for Parkinson’s to clinical trial within the next few years.
There are two types of cells which are currently being developed for clinical testing in dopamine replacement cell transplantation for Parkinson’s. Embryonic stem cells (or ESCs) – which are collected from IVF tissue donation – and induced pluripotent stem cells (or iPSCs) – chemically reprogrammed cells, usually from adult skin tissue and blood cells. Both types of cells are capable of becoming almost any cell in the body, and scientists have been working on recipes for turning them into dopamine-producing cells. These significant trials are underway.
Induced Pluripotent Stem Cells
Transplantation is not the only application for iPSC cells. Scientists are making iPSC’s from patients with Parkinson’s and using them in the lab for disease modelling purposes. These neurons act as a powerful tool to study the neuropathology of Parkinson’s and they can be used to test substances developed into new drugs to effectively treat the condition.
The MRC Centre for Regenerative Medicine, University of Edinburgh
Prof. Tilo Kunath’s laboratory in Edinburgh is leading the way here and Cure Parkinson’s is providing funding for this research. Prof. Kunath is producing pure batches of dopamine neurons under a highly technical process that only a few laboraties in the world are capable of doing safely and effectively to better differentiate and characterise the cell lines which are planned to be used for transplantation.
Cure Parkinson’s is also funding a study led by Prof. Roger Barker, which involves converting a person with Parkinson’s own skin cells directly into neurons. These cells are called induced neuronal cells (or iN cells). The goal of the study is to provide a rapid method of growing patient-specific cells, which would allow for a more personalised form of testing potential Parkinson’s therapies in the laboratory.
The California Institute for Regenerative Medicine (or CIRM) is a major funder of research focused on stem cell treatments and has agreed to provide $4 million to Ryne Bio to help bring their dopamine producing cell replacement therapy into the clinic for Parkinson’s.
The Michael J Fox Foundation awarded grants to the ASU-Banner Neurodegenerative Disease Research Center for a clinical trial testing transplantion of human iPSC derived dopamine neurons into the brains of people with a special type of Parkinson’s due to Parkin mutations. This project will be in collaboration with the van Andel institute and Fujifilm Cellular Dynamics.
Although there is a lot of excitement surrounding dopamine cell replacement therapy, we must proceed with care. The field has potential for setbacks from some of the less rigorous work being undertaken where regulatory standards are not as stringent as they perhaps should be or not meet the standards set by GForce-PD. These have the potential to halt proceedings on all cell replacement therapies.