Replacing cells lost in Parkinson’s by converting their neighbours

Groundbreaking research has developed a new technique that makes it possible to convert neighbouring brain cells into new dopamine-producing cells.

The research was conducted in mice. You can read the full research paper on the Springer Nature website. 

There are still many challenges to overcome before this technique can be tried in people with Parkinson’s but it opens the door to the development of an exciting new treatment approach.

Professor David Dexter, Director of Research at Parkinson’s UK, said:

"Cell transplants have, for a long time, aimed to replace lost cells in Parkinson’s but their effectiveness has been limited since they struggle to integrate and function effectively within the brain.

"This new technique has overcome this major hurdle in mice and opens the door to an exciting new treatment approach, which may be able to reverse Parkinson’s in people in future.

"While people affected by Parkinson’s should be greatly encouraged by the rapid advances researchers are making, such new technology requires extensive additional research and safety testing before it can be trialled in humans."

How could this work in people with Parkinson’s?

Replacing the dopamine-producing cells that are damaged and lost over time in the brains of people with Parkinson’s is not a new idea. Researchers have been working on possible ways to do this for decades.

However, most approaches to date have involved using stem cells to grow new healthy dopamine-producing cells in the lab with the aim of transplanting these into the brain later.

These transplantation based techniques hold great promise but there are significant challenges. Transplanted cells are at risk of rejection, struggle to fully integrate with existing networks and can fall victim to the same damage as the original cells.

This new approach offers hope for replacing these precious cells from within by calling on astrocytes, star-shaped cells found throughout the brain that play a multitude of roles, and converting them directly into dopamine-producing cells.

The technique reversed movement problems in mice which had been treated with a chemical that damages dopamine-producing cells and causes them to develop Parkinson’s-like symptoms such as slowness and problems with coordination and balance.

It’s important to stress that this technique has so far only been successfully tested in mice and will require much further development before it can be tried in people with the condition.

How does it work?

Astrocyte cells in the part of the brain affected in Parkinson’s will naturally develop into dopamine-producing cells when levels of PTB, a protein inside the cell which acts like a handbrake on this development, are decreased.

In these recent studies, the scientists developed a small molecule called RNA that provides instructions for cells to turn off the production of PTB.

They inserted this RNA into a harmless virus which can enter astrocytes and reprogram the cell to switch off the production of PTB.

Without the PTB handbrake on, the astrocyte naturally develops into a dopamine-producing cell.

Researchers at the University of California San Diego tested the technique in human cells in a dish and then in mice that had been treated with a chemical that damages dopamine-producing brain cells and causes Parkinson’s-like symptoms.

The researchers administered the treatment directly to the area of the mouse brain which is damaged in Parkinson’s.

In the treated mice, a small percentage of astrocytes were successfully converted, increasing the number of dopamine-producing cells by approximately 30%.

This was enough to restore dopamine levels to those seen in normal mice.

Within 3 months, the Parkinson’s-like symptoms had disappeared and the mice remained symptom free.

How long before this therapy can be tried in people with Parkinson’s?

There are a number of very important questions to be answered through further research to refine these techniques and fully understand their safety before they are ready to be tested in people.

These include:

• understanding whether cells that are converted using this technique survive and continue to function safely and effectively long-term
• understanding whether reducing the numbers of astrocytes in the brain causes any problems or side effects
• finding ways to target astrocytes in particular brain regions that are affected in Parkinson’s
• exploring how well these techniques may work in older brains
• understanding any potential side-effects and risks of this technique.

It is very difficult to predict how long this research and development will take but usually developing therapies to the standards required to be tested in people takes between 5 and 10 years.