The world’s first clinical trial using iPS cells in Parkinson’s disease
Original article: Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease: Dawn of a New Era. Cell Stem Cell: November 2, 2017.
Major progress is being made as a result of coordinated international efforts to develop safe and robust protocols for stem cells, so that new dopamine neurons can replace those lost to Parkinson’s. The difficulty has been sourcing the tissue for these cells. Recently, efforts have focused on reprogramming adult cells from skin or blood, and are now coming to fruition.
Why is it important?
The world’s first clinical trial using reprogrammed adult cells is due to begin in 2018.
As a therapeutic strategy, replacing the specialised dopamine neurons lost in Parkinson’s has several advantages over replacing dopamine with drugs which can lead to the development of dyskinesias and other unwanted symptoms. TRANSEURO is a Europe-wide trial set up to address inconsistent results from previous trials, and demonstrate the potential for dopaminergic cell replacement to be carried out safely and consistently, with good clinical outcomes. Among its aims is the development of a robust protocol that can serve as a template for all future trials in this field. However, sourcing the necessary fetal tissue for these transplants is a significant rate limiting step due to both ethical and logistical issues. As such, developing a safe, scalable and ethically acceptable source of cells is a major challenge.
More recently, new, renewable sources of tissue that can be grown into dopaminergic progenitor cells and eventually into dopamine neurons are gaining prominence: human pleuripotent stem cells (hPSCs) can be derived from early pre-implantation embryos (ESCs) or reprogrammed adult somatic cells (iPSCs).
The major research networks that have been developing these techniques joined forces in 2014 to form GForce-PD, a dynamic consortium dedicated to moving stem cell therapies for Parkinson’s forward in unison. Each of the teams, based in Europe, the US and Japan, is establishing reproducible and scalable protocols for the production of these cells that meet Good Manufacturing Practice (GMP) standards. GForce-PD is continually tackling important open questions around stem cell therapies for Parkinson’s. For example, a critical issue is the level of genetic and other checks this tissue should undergo, to ensure it is viable and safe to transplant. Other important issues include optimising immunosuppressive regimes for future clinical trials, deciding what criteria define the best candidates for the first human trial, what should be included in the optimal patient assessment protocol, and what comparisons the optimal trial design should include.
The first human clinical trials within this consortium are scheduled to begin this year (2018). Indeed, the world’s first clinical trial using iPS cells in Parkinson’s disease will be beginning in a few weeks’ time in coordination with Kyoto University Hospital, following a recent press release (see link).
Coordinating and regulating this work internationally to ensure safety, efficacy and reproducibility is key to the success of efforts which began more than 25 years ago, and will be coming to fruition within the next 3-5 years.
Original article:Barker, R. A., Parmar, M., Studer, L., & Takahashi, J. November 2, 2017. Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease: Dawn of a New Era.