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New neuron reprogramming technique could hold key to curing Parkinson's disease, say scientists

Researchers discover way to modify brain cells to address lack of dopamine

Katie Forster
Monday 10 April 2017 15:58
The condition, which is caused by a lack of dopamine in the brain, affects one in 500 Britons (Alamy)
The condition, which is caused by a lack of dopamine in the brain, affects one in 500 Britons (Alamy)

A “hugely promising” new technique in which brain cells are reprogrammed could one day provide a cure for Parkinson’s disease, experts have said.

Scientists at the Karolinska Institute in Sweden have discovered a way to modify neurons in the brains of people with Parkinson’s, a progressively worsening disorder of the nervous system that affects one in 500 people in the UK.

The disease, which can cause slow movement and involuntary shaking, is a result of a lack of dopamine, a chemical that acts as a messenger in the brain.

For decades, researchers have been trying to develop a treatment that involves transplanting dopamine neurons grown in a laboratory directly into the brain.

But this new approach, described in the journal Nature Biotechnology, “offers a completely new way to replace cells that are lost in Parkinson’s”, said Professor David Dexter, deputy director of research for the charity Parkinson’s UK.

“This research is hugely promising,” said Prof Dexter. “Replacing the cells that are lost in Parkinson’s is a possible way to reverse its symptoms, and could one day be a cure for the condition.”

The researchers were able to change common brain cells known as astrocytes into cells resembling dopamine neurons after testing a number of genes known to play a role in the creation of dopamine.

Four of the genes, when mixed in a microscopic “cocktail” with certain small molecules, reprogrammed both human neurons grown in a dish and similar cells in the brains of mice.

“What’s new in this study is that we used programming to turn an astrocyte into a neuron that is functional in people,” Ernest Arenas, who led the research, told The Independent.

“We’ve been working on this for six years, it’s been a long project,” he said. “It’s the absolute very first prototype of this type of strategy and we don’t know yet what the problems might be on the way to developing a cure in future. The focus was on demonstrating it's possible.”

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Prof Dexter called for further development of the technique, “so it encourages dopamine to be produced and released in a controlled manner, like the original brain cells”.

At the moment, “the location of the new cells created through this process could make it difficult to control the delivery of dopamine to the brain,“ he said. “If successful, it would turn this approach into a viable therapy that could improve the lives of people with Parkinson’s and, ultimately, lead to the cure that millions are waiting for.”

It is unclear what exactly causes Parkinson’s, although it is believed to be a combination of genetic and environmental factors.

The symptoms of the disease mostly affect people over 50, although one in 20 people with the condition first experience symptoms under the age of 40, according to the NHS.

Patrick Lewis, associate professor in cellular and molecular neuroscience at the University of Reading, said the study represents an advance in research into Parkinson’s treatments. “This study builds on previous research showing that mouse astrocytes could be converted into dopamine neurons, so in some ways the results of this study aren’t surprising – but the challenge of moving from mouse to human cells shouldn’t be underestimated, so this does represent a step forward,” he said.

Dr Lewis added: “A key test of whether newly derived dopamine neurons are functional is whether they can replace these cells in animal models that have a similar dopamine deficit to that seen in humans with Parkinson’s.

“The authors have shown that they can use this technique to correct some, but not all, of the symptoms seen in one of these mouse models so there is clearly some way to go before this approach can be used to fully compensate for dopaminergic cell loss in a mouse.”

Christopher Morris, a senior lecturer in neurotoxicology at Newcastle University, said: “The only thing that the researchers haven’t perhaps done is to show that the new nerve cells actually produce and release dopamine, although that is probably simply a matter of time to do those experiments”

“Given that a reasonable number of mice have been used in the study, the data from the mice looks sound and suggests that the treatment works for the mice, at least in the short term,” he said.

“What would also be useful to find out is how the new cells function in the long term – can they still help the mice after several months?

“We also know from previous human studies that new nerve cells when transplanted into the brain still degenerate and develop the pathological changes of Parkinson’s disease. This will therefore be a major hurdle.”

Dr Morris said that as delivering the new treatment could involve major surgery, “it may only be for people who have very severe problems associated with Parkinson’s. “An alternative would be to alter how the treatment is delivered to the brain and to find a novel way of doing this.”

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