Tuesday November 8 2011
Parkinson's causes the death of key cells in the brain
New stem cell research may point to ways of replacing the brain cells that die off in Parkinson’s disease, The Guardian recently reported.
In the research, scientists were able to use human stem cells to create dopamine neurons, which have similar properties to the types of brain cells lost in Parkinson’s disease. When the scientists introduced the new cells into the brains of mice, rats and monkeys with Parkinson’s-like lesions, the animals were able to survive, and in the mice and rats the movement problems normally seen were reversed. In addition, no cancer or uncontrolled cell growth were seen after the cells had been introduced: two safety concerns associated with stem cell therapy.
The results of this study are extremely promising, although more work is required before stem cell-based therapy can be used to treat Parkinson’s disease in humans. That said, the neurons which the researchers have created could have immediate applications in research, such as being used in cell-based models of Parkinson’s disease. This in turn could help find a cure for Parkinson’s disease, such as developing new drugs faster.
Where did the story come from?
The study was carried out by researchers from the Memorial Sloan-Kettering Cancer Centre, New York and several other American research institutions. It was funded by the US National Institutes of Health, the US National Institute of Neurological Disorders and Stroke, the European Commission NeuroStemcell project and several other research funds. The study was published in the peer-reviewed journal, Nature.
This story was covered by The Guardian, which accurately presented the research and included passages and images making it clear that the research was performed in animals. The newspaper also included quotes from Parkinson’s UK and seemed to imply that stem cell therapy is still some way off, but that this finding is promising for the future.
What kind of research was this?
This was a laboratory-based and animal study. The authors aimed to develop a method that would allow them to create human dopamine neurons (types of brain cells that die in Parkinson’s disease) from human stem cells. They then wanted to test whether these neurons could be used to reverse the signs and symptoms of Parkinson’s disease in animal models.
These sorts of questions can only be answered by laboratory and animal-based studies. Only once the technique has been thoroughly tested and evaluated through a significant amount of animal research can it be considered for use in small, experimental human trials.
What did the research involve?
The researchers used recent research on dopamine neurons to develop a new laboratory-based protocol to create them from stem cells. They then tested the features of the cells that they created to see whether they were similar to the dopamine neurons found within the midbrain (the part of the brain where Parkinson’s disease occurs).
The researchers then wanted to test whether the dopamine neurons they created could survive if introduced into the brains of animals. They also wanted to check that there was no risk of “neural overgrowth” (in other words, a potentially harmful overproduction of new brain cells), and that the cells they introduced did not form the incorrect cell type. The researchers then determined whether the cells they had created in the laboratory could repair the damage seen in animals with Parkinson's-type lesions.
The animal models had been created by treating the animals with specific chemicals, as Parkinson's disease is not known to occur in any species other than humans.
What were the basic results?
The researchers managed to develop a method that would allow them to create dopamine neurons which were very similar to the dopamine neurons normally found in the midbrain. They found that these neurons could survive when injected into the brains of healthy mice, and did not overgrow (where they continue to grow abnormally) after injection. The dopamine neurons also successfully grafted in the brains of mice and rats treated with chemicals to create models of Parkinson’s disease.
These introduced neurons reversed the movement problems seen in these animals. Finally, as the number of dopamine neurons required in a mouse or rat is much lower than the number needed in a human, the researchers investigated whether the technique could be scaled up to treat two monkeys with Parkinson’s-like lesions. Again, the neurons successfully grafted into the brains of two monkeys.
How did the researchers interpret the results?
The researchers conclude that the "excellent dopamine neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson’s disease".
In this study, researchers managed to create dopamine neurons from human stem cells. These neurons were very similar to the neurons found in the midbrain, and therefore were very similar to the neurons lost in Parkinson’s disease. The cells they created were able to survive when introduced into the brains of mice, rats and monkeys with Parkinson’s-like lesions, and reversed the movement problems seen in mice and rats. No problems with neural overgrowth were seen.
The results of this study are extremely promising, but much more work is required before stem cell-based therapy can be used to treat Parkinson’s disease in humans. For example, although the animals regained movement, the complexity of the human brain is greater than that seen in the animals tested. It would need to be determined whether the use of stem cells in this way might negatively affect higher functions such as speech or complex memory.
Also, there other points to consider, such as how closely the chemically induced brain changes experienced by the animals represented Parkinson’s disease, and whether the use of stem cells in this way would be safe or effective in the long-term.
However, the neurons that the researchers have created could also have useful and important applications for research in this area. In particular, cell-based models of Parkinson’s disease could now be created and used for tasks such as developing new drugs faster.
The Guardian notes that doctors have already tried transplanting foetal brain tissue into Parkinson's patients in the 1990s with inconsistent or unpleasant results: some patients got better while others experienced runaway involuntary movements. In these cases, the timing of the transplant seemed to be important and it is possible that this new technique, which did not produce “cellular overgrowth”, will in time lead to further transplants that are safer.