Accidental Discovery Cured Mice With Parkinson’s Disease

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

Over 145,000 UK residents were believed to be living with Parkinson’s disease in 2018, and in America nearly 1 million people are thought to have the disease. There currently is no known cure for this disease, existing treatments are geared towards easing the symptoms of the disease to help improve quality of life. Now these scientists have used their discovery to develop a one off treatment that suggests to have eliminated mice of the symptoms of this disease, which is raising hope of eventually finding a cure for humans in the future. 

The scientists were investigating PTB proteins that turn genes on/off within cells; to better understand how it influences cell functions the protein was silenced in the connective tissues of cell fibroblasts which were then grown in petri dishes to examine for any changes. A few weeks later the scientists discovered that few fibroblasts remained, they were replaced largely by neurons. In another experiment published in the journal Nature the team also discovered that astrocytes brain cells also converted 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.”

Next the team turned their attention to Parkinson’s disease, exposing rodents to chemicals that create symptoms of the disease; after silencing PTB 30% of their astrocytes were observed to turn into nerve cells reaching levels comparable to those in normal animals, and the new neurons appeared to grow as normal sending new connections to other parts of the brain. Symptoms of the disease were completely restored to normal movement in the animals after turning off PTB with just one treatment lasting for the animal’s lifespan. 

“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.”

Next the team plans to silence PTB in mice via genetic changes that cause Parkinson’s disease like symptoms rather than dopamine poisoning. 

While this comes as very promising news, it was noted that much more rigorous testing is required before this approach can be tested in humans. “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.

“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.

“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,” said Professor Tara Spires-Jones from the University of Edinburgh.

“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.”

“Research is the only way we can end the fear, heartbreak and harm that diseases like Parkinson’s cause,” added Dr Imarisio. Prior to this current outbreak scientists in Parkinson’s UK believed they were close to a breakthrough, but since then the charity has been forced to “fight for fair treatment and better services” for patients, who are more at risk of coronavirus complications.

Robert Howard, professor of old age psychiatry, at University College London, said the findings were an “extraordinary scientific discovery” adding that : “This opens up a completely novel avenue for development of treatments to ‘rebuild’ damaged brains in Alzheimer’s and Parkinson’s diseases.”