New hope for treating Parkinson’s disease as novel stem cell trial prepares to launch in Japan

On July 30th, researchers in Japan announced their intention to launch a new clinical trial using neurological cells derived from induced pluripotent stem (iPS) cells to treat Parkinson’s disease, a neurodegenerative disorder that mainly affects dopaminergic neurons, the dopamine-producing cells in the brain. The recruitment notice was posted by the Kyoto University Hospital at 5 pm (local time).

Parkinson’s causes programmed death ― a process known as apoptosis ― of dopaminergic neurons. While it’s still not well understood why this happens, the resulting lack of dopamine can lead to a severe reduction in motor skills causing difficulty walking as well as uncontrollable trembling. The cell type researchers plan to inject are precursors to these dopamine-generating neurons. Cells will be injected directly into the putamen ― a round structure at the base of the forebrain ― which is the area known to play a central role in Parkinson’s-associated neural degeneration.

The cells will come from a stock of healthy donor cells, which is a much faster and more cost-effective route than using the patient’s own cells. Moreover, patients will be immunologically matched with suitable donor cells to minimize the risk of immune rejection and will also receive immnunosuppressant drugs alongside the injections.

The trial is based on previous animal studies, including one published in 2017 in Nature showing significant improvements in Parkinson’s symptoms, lasting up to two years, after monkeys received injections of iPS-derived neurons (1). Once injected the progenitor cells were shown to differentiate into dopaminergic neurons and engraft in the brain.

First pioneered in the lab of Prof Shinya Yamanaka, iPS cells are adult somatic cells that have been reprogrammed into pluripotent stem cells ― with the ability to differentiate into any cell specialized type ― by using four gene-encoding transcription factors (2). Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for the discovery, together with Sir John Gurdon for his earlier work on cloning.

This is not the first time IPS cells are being tested in the clinic. Ongoing clinical trials using retinal cells derived from iPS cells to treat age-related macular degeneration (AMD) are in progress since 2014 led by Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe. So far, the iPS cell-derived AMD treatment has been deemed safe with only one adverse reaction reported (3).

Researchers have long tinkered with the potential of using stem cells to restore dopamine production. Moreover, the use of IPC cells instead of embryonic cells would mean the treatments could be made available in countries where the use of embryonic tissue is banned. Results of the trial will be met with much anticipation from both the research and medical community, and most importantly, the patients battling degenerative diseases like Parkinson’s as well as their friends and families.

(1) Kikuchi T. et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature (2018). DOI: 10.1038/nature23664

(2) Takahashi K. and Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell (2006). DOI: 10.1016/j.cell.2006.07.024

(3) Normile D. iPS cell therapy reported safe. Science (2017). DOI: 10.1126/science.355.6330.1109