Towards Transplantation of Stem Cell Derived Neurons for Parkinson's Disease
The more obvious manifestations of Parkinson's disease stem from the the loss of a small population of dopamine-generating neurons. These cells are more sensitive to the underlying pathology of α-synuclein protein aggregation that drives the condition. Researchers have been working towards cell therapies that deliver new neurons for a long time now. A variety of clinical trials are underway, using a variety of cell sources; here, one of those programs has advanced to the stage of a first treated patient. None of these programs have yet emerged into widespread clinical practice. Is replacing cells the best way forward in this condition? It seems likely that ways to remove the toxic protein aggregates would be more beneficial, given that (a) they are causing other harms, and (b) transplanted cells will likely succumb to the same environmental issues caused by the aggregates.
There are around eight million people living with Parkinson's disease globally; a disease which involves loss of dopamine nerve cells deep in the brain, leading to problems in controlling movement. The standard treatment for Parkinson's disease are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects. As of today, there are no treatments that can repair the damaged structures within the brain or that can replace the nerve cells that are lost.
The STEM-PD trial is now testing a new investigational therapy aimed at replacing the lost dopamine cells with healthy ones manufactured from stem cells. The cell product that is being used has been subjected to rigorous pre-clinical tests. After being transplanted, the cells are expected to mature into new and healthy dopamine producing nerve cells within the brain. On 13th of February 2023, a transplant of stem cell-derived nerve cells was administered to a person with Parkinson's. The product is being tested in patients for the first time. The transplantation product is generated from embryonic stem cells and functions to replace the dopamine nerve cells which are lost in the parkinsonian brain.
This patient was the first of eight with Parkinson's disease who will receive the transplant. The patients in the trial were diagnosed with Parkinson's at least ten years ago and are at a moderate stage of their disease. The researchers will follow these patients closely and assessments of cell survival and potential effects will be conducted over the coming years.
"..It seems likely that ways to remove the toxic protein aggregates would be more beneficial"
maybe 2 pronged approach, i.e. clean up environment by first removing aggregates before replacing lost cells?
There are at least three trials using either human embryonic stem cells or induced pluripotent stem cells derived dopamine progenitors have dosed their first patient. They aim to improve motor symptom, and probably will do nothing for the non-motor symptom. However, they can be amazing at improving the motor symptoms if you look at the previous fetal cell trials.
hESCs or hiPSCs derived neurons resembles fetal neurons, so they are quite resilient and it will probably take them years to develop any pathology in the patients. All of these neurodegenerative diseases are quite complicated. It's unclear if symptoms can be improved by just removing the protein aggregates --> Look at all the trials using this strategy to treat Alzheimer.