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Mice ‘cured’ of Parkinson’s in accidental scientific discovery

Mice were “cured” of Parkinson’s disease after a scientific study took an unexpected turn.

Alexandra Thompson, Yahoo.com, Jun 29, 2020

Scientists from the University of California (UC) in San Diego set out to better understand the role of proteins in connective cells, only to discover a way to transform many different types of cells into neurons.

Parkinson’s comes about when neurons - nerve cells - that produce the chemical messenger dopamine, which regulates movement, die off. Patients typically suffer tremors, slow movement and loss of balance when 80% of dopamine is lost.

The scientists used this discovery to develop a one-off treatment that eliminated Parkinson’s symptoms in mice, raising hopes of a cure down the line.

Existing treatments aim to ease signs of the disease and improve a patient’s quality of life, like via physiotherapy.

‘I was stunned at what I saw’

More than 145,000 people over 20 in the UK are thought to have been living with Parkinson’s in 2018. In the US, nearly 1 million people have the disease.

The UC scientists were studying a protein called PTB that turns genes “on or off” within cells.

In an attempt to better understand how PTB influences cell function, they silenced the protein in the connective tissue cell fibroblasts.

The fibroblasts were then grown in petri dishes to check for any changes.

A couple of weeks later, the scientists were surprised to find very few fibroblasts remained, having largely been replaced by neurons.

In a later experiment, published in the journal Nature, the team discovered brain cells called astrocytes also “turned” into neurons when PTB was silenced.

“Researchers around the world have tried many ways to generate neurones in the lab, using stem cells and other means, so we can study them better, as well as to use them to replace lost neurones in neurodegenerative diseases,” said lead author Dr Xiang-Dong Fu.

“The fact we could produce so many neurones in such a relatively easy way came as a big surprise”.

The scientists then turned their attention to Parkinson’s.

Rodents were exposed to a chemical that poisons dopamine-producing neurons, creating symptoms of the disease.

After silencing PTB, 30% of the mice’s astrocytes turned into nerve cells, reaching levels comparable to those in normal rodents.

These new neurons seemed to grow as normal and even sent connections to other parts of the brain.

When it came to symptoms, turning off PTB completely restored normal movement in the mice, with just one treatment lasting throughout their life.

“I was stunned at what I saw,” said co-author Dr William Mobley.

“This whole new strategy for treating neurodegeneration gives hope it may be possible to help even those with advanced disease”.

Professor David Dexter from Parkinson’s UK added: “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.”

‘Critical progress is at stake’ due to coronavirus

Although promising, much more rigorous testing is required before the approach can be tested in humans.

The scientists plan to silence PTB in mice with genetic changes that cause Parkinson’s-like symptoms, rather than the disease coming about via dopamine poisoning.

“Advances in technologies like this are vital and this is promising and well-conducted early-stage research, but it is in mice and it’s not yet clear whether this approach could be used in people,” said Dr Sara Imarisio from Alzheimer’s Research UK.

Neurons are also destroyed in Alzheimer’s disease.

“Further research will need to develop a better understanding of the potential adverse effects of converting these cells in this way before we can know whether this technique is even possible in a human brain,” said Dr Imarisio.

Professor Tara Spires-Jones from the University of Edinburgh added: “While the principle of this study is remarkable and promising, it is important to note that it was conducted in mice with group sizes from three to eight and there is a long way to go to translate this into a treatment for people.”

Nevertheless, the UC team has patented their treatment in the hope it could one day help patients.

“It’s my dream to see this through to clinical trials, to test this approach as a treatment for Parkinson’s disease, but also many other diseases where neurones are lost, such as Alzheimer’s and Huntington’s diseases and stroke,” said Dr Fu.

“Dreaming even bigger, what if we could target PTB to correct defects in other parts of the brain, to treat things like inherited brain defects?

“I intend to spend the rest of my career answering these questions.”

While it all sounds promising, medical research charities in the UK have warned “patients will suffer the consequences” unless they receive government support amid the coronavirus outbreak.

“Findings like this do highlight the potential of medical research, but critical progress is at stake and it’s essential that dementia research is backed by the government throughout the COVID-19 crisis,” said Dr Imarisio.

COVID-19 is the respiratory disease that can be triggered by the coronavirus.

“Research is the only way we can end the fear, heartbreak and harm that diseases like Parkinson’s cause,” added Dr Imarisio.

Prior to the pandemic, Parkinson’s UK “knew” a major breakthrough and cure for the disease was “close”.

Instead, the charity has been forced to “fight for fair treatment and better services” for patients, who are more at risk of coronavirus complications.

To maintain this increased support, Parkinson’s UK must reportedly raise £95,000 ($118,872) a week for the next three months.

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