Image courtesy of: Dr Tilo Kunath, MRC. Image shows stem cell-derived dopamine-producing neurons. Red is a marker for neurons and green a marker for Parkinson’s pathology (phospho-Serine-129 alpha-synuclein).

Scientists at the MRC Centre for Regenerative Medicine (University of Edinburgh)- led by Dr Tilo Kunath and part-funded by The Cure Parkinson's Trust (CPT) - have published a research report demonstrating that genetically reducing alpha synuclein, using gene editing, results in a measure of resistance to one of the pathological hallmarks of Parkinson's.

The accumulation (or aggregation) of the protein alpha synuclein is considered to be one of the characteristic features of the Parkinsonian brain. Over time, clusters of the aggregated protein form what are called Lewy bodies in specific regions of the brain in Parkinson's (PD). This aggregated form of the protein is believed to have a toxic effect on neurons, and it has been proposed that PD may progress by aggregated alpha synuclein being passed from one neuron to the next. This latest development addresses limitations in the treatment in which, over time, transplanted tissue can acquire signs of disease from nearby neurons.

Researchers at the University of Edinburgh have created stem cells that are resistant to developing Parkinson’s. They snipped out sections of DNA from the human cells in the lab using the advanced technology known as CRISPR/Cas9n mediated gene editing. In doing so, they removed a gene linked to the formation of the toxic clumps or Lewy bodies.

What Dr Kunath's research has demonstrated is that by reducing/removing normal alpha synuclein protein in neurons exposed to clumps of alpha synuclein, there is a significant reduction in the accumulation of toxic aggregated alpha synuclein in those cells. Dr Kunath said:

We know that Parkinson’s disease spreads from neuron to neuron, invading healthy cells. This could essentially put a shelf life on the potential of cell replacement therapy. Our exciting discovery has the potential to considerably improve these emerging treatments.

We know from previous clinical trials of cell transplanation approaches for Parkinson's that Lewy bodies can start to appear in the transplanted neurons over time supporting the idea that the disease is being passed between neurons. The results of this new research suggests that by transplanting dopamine neurons with low levels of normal alpha synuclein protein, we may be able to reduce the likelihood that these neurons will develop the aggregated alpha synuclein in the form of Lewy bodies.

“Cell replacement therapy represents one experimental approach to regenerative medicine for people with Parkinson's. This new research by Dr Tilo Kunath and his team at the University of Edinburgh provides another advancement in the development of this treatment. The Cure Parkinson's Trust is thrilled to be associated with this inspiring and innovative research.

Dr Simon Stott - Deputy Director of Research, CPT

Read the full press release here.