Parkinson’s gene editing breakthrough in mice offers hope for patients – their damaged neurons could be replaced

Scientists have discovered a way to convert mouse brain cells into neurons, replacing those damaged by disease
This could lead to a one-step strategy to treat a number of degenerative diseases that affect millions of people

Wellness

Agence France-Presse

Published: 5:15pm, 26 Jun 2020

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Scientists have discovered a “one-step strategy” offering hope for treating Parkinson’s disease and other degenerative illnesses after converting mice brain cells into functioning neurons, they reported this week.

The motor defects associated with Parkinson’s are largely caused by the loss of dopamine-emitting neurons – electrically active cells that communicate with others – in the brain. A team of US- and China-based researchers used genome editing to convert a different type of brain cell – glial cells called astrocytes, for their star shape – into neurons, slowing the loss of dopamine and restoring motor functions in injured mice.

Past attempts to treat neurodegenerative disorders such as Parkinson’s have aimed to prevent or slow the loss of dopamine-emitting neurons, which do not naturally repopulate when they die or become damaged. The new technique simply aims to replace them through cell conversion, scientists said.

“We’re now rebuilding the whole pathway,” Xiang-Dong Fu, a professor at the University of California, San Diego, said. “That becomes a very promising approach to turn non neuronal cells into neurons to replace those lost ones.”

Cellular and molecular biologist Xiang-Dong Fu is a professor at the University of California, San Diego. Photo: Fu Lab

Worldwide, about seven per cent of people over 65 suffer from Alzheimer’s or some form of dementia, a percentage that rises to 40 per cent above the age of 85. More than 10 million people live with Parkinson’s.

Researchers were able to convert astrocytes – a type of brain cell similar to neurons – in the part of the brain where Parkinson’s causes neuron loss into dopamine-emitting neurons by removing an RNA-binding protein called PTBP1.

The gene editing can turn brain glial cells (above) into neurons. Image: Shutterstock

“We stumbled into this phenomenon,” said Fu, a cellular and molecular biologist who studies RNA, the molecule that codes DNA. “When you deplete this protein, practically any cell we tested became neurons.”

While astrocytes are prevalent in the brain, the PTBP1 protein prevents them from naturally being converted into neurons. The team used CRISPR genome-editing techniques to reprogramme the astrocyte RNA, then inject it into different parts of the mice brains. Three out of four mice that received the cell conversion therapy showed “significant restoration of dopamine release,” they wrote in the journal Nature.

The researchers performed studies on 2-month-old and year-old mice – the human equivalent of testing 20-year-olds and 60-year-olds.

Scientists turn astrocyte cells into neurons (above) by removing an RNA-binding protein called PTBP1. Image: Shutterstock

While the cell conversion was highly successful in the younger mice, the authors reported an “age-related decrease” of success in older animals. “The ageing issue is a big problem,” he said. “Not only is the disease age-dependent, but a lot of things are age dependent, including the ability to switch cell fate.”

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Another challenge is increasing the effectiveness of the cell conversion rate. Ernest Arenas, a professor of molecular neurobiology at the Karolinska Institute in Sweden, wrote in a linked editorial that 60 to 65 per cent of the infected astrocytes did not convert to become neurons. “This percentage must decrease,” he said.

“Eventual application of our approach to humans will need to overcome many obstacles,” the authors wrote, noting that in addition to age-related limits, more research about potential side effects of the treatment as well as the impact of astrocyte depletion on brain function would need to be done.

Ernest Arenas is a professor of molecular neurobiology at the Karolinska Institute in Sweden. Photo: Karolinska Institute

Fu cautioned that applying the cell conversion technique to humans was still a distant possibility, and that additional research in larger animals such as rats and monkeys would be needed first.

“This mouse study is just the beginning,” he said. “It’s the proof of a concept. Clearly we cannot get overexcited and just say, ‘Tomorrow, let’s shoot these things into human brains,’ and then the next day everybody’s fine,” he added. “That would be too magic.”

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