http://www.mirror.co.uk/lifestyle/health/parkinsons-breakthrough-experiments-show-brain-10197226

Parkinson’s breakthrough as experiments show brain cells killed by the disease can be replaced
Experiments on human cells and mice have shown they can be re-created by converting other brain cells, which raises the prospect of gene therapy without the need for cell transplantation

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Brain cells killed off by Parkinson’s disease have been replaced in a breakthrough that could offer fresh hope to sufferers.

The neurons produce dopamine, a chemical that controls movement. When these are lost it leads to devastating tremors and co-ordination difficulties.

Now experiments on human cells and mice have shown they can be re-created by converting other brain cells called astrocytes into those that resemble dopamine neurons.

The breakthrough raises the prospect of gene therapy for Parkinson’s patients without the need for cell transplantation.

The research published in Nature Biotechnology identified four genes that – when combined with certain molecules – re-programmed the astrocytes which are star-shaped cells crucial in the maintenance of normal brain function.

In tests the method improved the physical function of mice with a rodent form of Parkinson’s. Scientists say more work is needed before it can be tried on humans.

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10,000 people are diagnosed with Parkinson’s each year (Photo: Science Photo Library RF)
Dopamine neurons are destroyed in Parkinson’s which affects one in 500 people in the UK and involves parts of the brain that become progressively damaged over time.

Although most of the 10,000 people diagnosed each year are aged over 60, one in 20 is under 40. Figures in the US suggest it affects around a million adults.

The three main symptoms are involuntary shaking of particular parts of the body, slow movement and stiff and inflexible muscles.

Current drug treatments only deal with symptoms but don’t cure the disease or prevent it from worsening.

Most cases have no known cause but a defining feature is the progressive death of a specialised type of neuron that secretes dopamine.

A decades-long research effort is seeking to develop a therapy in which the brain cells would be generated in the laboratory and transplanted into the brain.

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The new approach by Professor Ernest Arenas and colleagues does not require cell transplantation.

it came about after they tested a number of genes known to be important for dopamine production.

Using a toxin they killed of dopamine neurons in mice and then delivered the four genes to the brain using a system designed to express them only in astrocytes.

The main symptoms are involuntary shaking, slow movement and stiff and inflexible muscles (Photo: Universal Images Group Editorial)
Some were successfully reprogrammed – acquiring characteristics of dopamine neurons and correcting several behavioural symptoms caused by loss of the brain cells.

Prof Arenas, of the Karolinska Institute in Stockholm, said: “Parkinson’s disease is a neurodegenerative disorder characterised by the progressive loss of dopamine neurons.

“Current treatments for the disease focus on symptomatic management through restoration of dopaminergic activity but do not alter the progressive neuro-degeneration.

“There is therefore a clear medical need for disease-modifying therapies.

“Cell replacement therapies for neuro-degenerative disease have focused on transplantation of the cell types affected by the pathological process.

“Here we describe an alternative strategy for Parkinson’s disease in which dopamine neurons are generated by direct conversion of astrocytes.

“With further optimisation this approach may enable clinical therapies for Parkinson’s disease by delivery of genes rather than cells.”

But he said further research would be needed before it could be considered for human trials.

Coronal view of a human brain in Parkinson’s disease (Photo: Cultura RF)
Prof Arenas said the finding that mouse astrocytes can be reprogrammed

to reverse motor behaviour problems of Parkinson’s supports future development

of the strategy “as a treatment for the disease.”

He said: “The next steps to be taken toward achieving this goal include improving reprogramming efficiency, demonstrating the approach on human adult astrocytes, developing systems to selectively target them and ensuring safety and efficacy.”

Parkinson’s takes hold as cells that produce dopamine die off in part of the brain called the substantia nigra.

This causes tremors, rigidity and slowness of movement, though patients may also experience tiredness, pain, depression and constipation, which worsen as the disease progresses.

The main treatments for Parkinson’s are drugs that aim to control the symptoms by increasing the levels of dopamine that reach the brain and stimulating the parts of the brain where dopamine works.

Some patients have wires surgically implanted into their brains that deliver electrical pulses to alleviate movement problems.

For around a decade, scientists have been trying to regrow nerve cells lost in neuro-degenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) from stem cells.

However experiments in which dopamine neurons were created from mouse stem cells have not been successfully reproduced in humans.

There have also been safety concerns, with signs that dopamine neurons developed from human stem cells can trigger the growth of tumours. As a result, clinical trials in humans have yet to start.

The latest study offers a new way of creating dopamine-producing brain cells that have been lost.

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