Brain cell reprogramming therapy shows promise for Parkinson’s


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"New technique in which brain cells are reprogrammed could one day provide a cure for Parkinson's disease," The Independent reports.


Researchers, using mice with Parkinson's disease, "reprogrammed" cells to replace the nerves lost in the condition. These nerves produce the messenger chemical dopamine, and help to coordinate body movements.


Parkinson's is a neurological condition, of unknown cause, where there is a progressive loss of dopamine-producing nerve cells in the brain. The gradual loss of these nerves leads to the symptoms of Parkinson's, such as tremor and muscle stiffness.


In this study researchers used an injection of a specially engineered virus to introduce a combination of genes into the brains of the mice. These genes were designed to target a type of cell known as astrocytes. These cells serve a wide range of functions, but crucially they do not carry electrical signals like nerve cells or produce dopamine.


This virus was also able to convert astrocytes within the brains of the mice into dopamine-producing cells (which the researchers called induced dopamine neurons (iDANs)). They saw improvement in some aspects of walking in these mice when they exercised on a treadmill.


Researchers hope their methods could eventually be used to treat humans with Parkinson's.


While these are promising findings, it may be premature to call this a breakthrough, as BBC News put it. As yet, we do not know whether this approach could be used to reverse symptoms in people with Parkinson's disease.


The effectiveness, and more importantly the safety of this approach in humans is currently uncertain.


 


Where did the story come from?


The study was carried out by researchers from the Karolinska Institutet, Medical University of Vienna, Malaga University and Stanford University. Funding was provided by a large number of institutions, including the Swedish Research Council, Swedish Foundation for Strategic Research and the Karolinska Institutet. There were no reported conflicts of interest.


The study was published in the peer-reviewed journal Nature Biotechnology.


The UK media's reporting of the study, aside from a slightly over-optimistic tone, was accurate and included useful commentary from independent experts.


 


What kind of research was this?


This was a laboratory experiment and animal study in mice and human brain cells. It aimed to investigate whether it is possible to modify cells commonly found in the brain (called glial cells – specifically a type called astrocytes) to replace those lost through Parkinson's disease. The researchers hope this approach could reduce or reverse symptoms.


The nerve cells lost in Parkinson's disease are in a part of the brain called the substantia nigra. They produce a chemical called dopamine, which transmits signals from these cells to other nerve cells. Dopamine belongs to the class of chemicals known as neurotransmitters.


Researchers have been studying different ways to replace these cells. In the past they have been able to convert adult mouse and human skin cells into dopamine-producing nerve cells in the laboratory.


However, these cells would need to be transplanted into the brain, a procedure which could pose a number of serious risks.


In the current study, researchers wanted to assess whether they could get cells already in the brain to convert into dopamine producing nerve cells, to avoid the need for transplantation.


Animal studies such as this are a useful way to carry out early stage research which can then be refined before testing in human trials. In this case human cells were also modified in the laboratory, which increases confidence that the technique might work in humans.


 


What did the research involve?


The researchers used genetic engineering to get the glial cells to switch on genes needed to become dopamine producing nerve cells. Researchers tested the effect of switching on a number of genes in human glial cells in the laboratory under a number of different conditions. They aimed to identify the combination that was most effective at getting the glial cells to become dopamine producing nerve cells.


Mice were engineered to have symptoms of Parkinson's by destroying their dopamine-producing nerve cells. Their brains were then injected with the combination of genes, contained within a virus, which had been identified in the first set of experiments, to see if this would convert their glial cells.


They were then analysed five weeks later to see if this modification had resulted in improvements to their motor (movement) skills.


 


What were the basic results?


The researchers found that they were able to get human glial cells in the laboratory to convert into dopamine producing nerve cells. They got the best results when they used a specific combination of four genes important in the development of these cells. They could get up to 16% of the glial cells to develop the characteristics of dopamine-producing nerve cells.


They then injected this specific combination of four genes into the brains of some mice with Parkinson's-like symptoms. After five weeks, the treated mice appeared to walk better on a treadmill compared to control mice.


 


How did the researchers interpret the results?


The researchers conclude their findings show that in mice it was possible to re-programme cells in the brain to replace the dopamine-producing nerve cells lost in Parkinson's disease. As a result of this they were able to reverse some of the symptoms of Parkinson's in a mouse model of the disease.


The researchers conclude: "The next steps to be taken toward achieving this goal include improving reprogramming efficiency, demonstrating the approach on human adult striatal astrocytes … in vivo [in an actual human, as opposed to a lab experiment], and ensuring safety and efficacy in humans."


 


Conclusion


This laboratory and animal study aimed to see whether it is possible to modify a type of cell commonly found in the brain, called glial cells, to become dopamine-producing nerve cells. These dopamine-producing nerve cells are the ones lost in people with Parkinson's disease. If a method could be found to replace these cells, it could potentially be used to treat the condition.


Previous research has shown that mouse and human skin cells can be converted to dopamine-producing cells in the laboratory. However, this is the first study to develop a way to convert a different type of cell already in the brain into dopamine-producing nerve cells. It has also shown that this can produce improvements in Parkinson's-like symptoms in a mouse model of the disease.


These findings are promising, particularly as the researchers have shown that it is possible to use this technique to modify human cells as well as mouse cells. However, the approach has not yet been tested in people with Parkinson's and it is not possible to know whether the cells would function as expected or whether the change would be long lasting.


Even before human studies can be carried out, it is likely that more animal experiments would be needed to ensure the approach is effective and safe in the long-term. 


Links To The Headlines

New neuron reprogramming technique could hold key to curing Parkinson's disease, say scientists. The Independent, April 11 2017


Brain cell therapy 'promising' for Parkinson's disease. BBC News, April 11 2017


Parkinson's breakthrough as experiments show brain cells killed by the disease can be replaced. Daily Mirror, April 11 2017


Links To Science

Di Val Cervo PR, Romanov RA, Spigolon G, et al. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model. Nature Biotechnology. Published online April 10 2017



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by GetDoc Team

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