Lab research

New mouse model highlights promising potential drug for slowing Parkinson’s

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The results indicate that, when given early, the molecule Anle138b may restore dopamine levels and help slow or stop Parkinson’s in its tracks.

Researchers at the University of Cambridge, funded by Parkinson's UK, have developed a new animal model and shown that anle138b may slow down the progression of Parkinson's by targeting toxic alpha synuclein-clumps.

Their results, published in Acta Neuropathologica, hint at a window of time where dopamine levels can be restored and cells can be rescued before any nerve cell loss occurs.

Targeting protein clumps

When Parkinson's develops, the protein alpha-synuclein forms sticky clumps in the brain known as Lewy Bodies, that are associated with nerve cell death and the motor symptoms of Parkinson's, including freezing, tremors and slowness of movement.

Anle138b has previously been shown to reduce the clumping of proteins in neurodegenerative conditions, including Parkinson's. But, in order to fully study the potential of anle138b for treating Parkinson's, the team first had to develop a way to better test it.

Mimicking Parkinson’s in mice

The researchers, led by Professor Maria Grazia Spillantini, created a new mouse model of Parkinson's that mimics the way alpha-synuclein gradually accumulates in areas of the brain affected by the condition.

After 9 months, the researchers found that levels of dopamine were reduced, with the mice developing symptoms that mimicked some of the subtle early motor symptoms seen in people with Parkinson’s such as the shuffling of feet when walking. By twenty months, the increasing clumps had led to the loss of 50% of the dopamine-producing nerve cells, causing more severe movement problems in the mice.

The team found that by treating the mice with anle138b after nine months, the drug reduced alpha-synuclein clumps, restored dopamine levels in the brain, prevented nerve cell death and reversed some of the subtle motor symptoms. These results suggest anle138b may be particularly effective at slowing, or even stopping, Parkinson’s if given early enough, before the nerve cells are lost.

Dr Beckie Port, Research Communications Manager at Parkinson's UK, said:

“The evidence from this early stage study builds on our understanding of how alpha-synuclein is involved in Parkinson's and provides a new model that could unlock future treatments.

“Additionally, the discovery that targeting alpha-synuclein aggregation early on can restore dopamine levels and rescue cells may prove to be crucial in stopping Parkinson's in its tracks.

“Today, we have no treatments that can slow or stop the progression of Parkinson's. It is vital we continue to support world-leading academics, like those in Cambridge, and ensure results like these are turned into future treatments that are so desperately needed for the 1 in 37 of us that will be diagnosed in our lifetime.”

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