Promising molecule targets proteins to give hope to people with Parkinson's disease

The results of a study published today on a molecule targeting clusters of alpha-synuclein, a key protein linked to Parkinson's disease, provide hope that it will will be possible to slow down or prevent the progression of the disease in humans.

Researchers at the University of Cambridge have been studying the effect of a molecule called anle138b by developing a new murine model of Parkinson's.

Founded by the charity Parkinson's UK, the study examined the effect of anle138b on the accumulation of alpha-synuclein, a protein known to form clusters tights, called Lewy bodies, in the brain. These clusters are badociated with the death of nerve cells responsible for dopamine production, which allows messages to be sent to parts of the brain that help coordinate movement. This causes the motor symptoms badociated with Parkinson's disease, including freezing, tremors and slow movements.

Anle138b has already demonstrated its ability to reduce protein clumping in neurodegenerative conditions, including other Parkinson's models. In order to further investigate the potential of the molecule for the treatment of the disease, researchers have created a new murine model of Parkinson's disease, replicating how syn-alpha-alpha accumulates progressively in areas of the brain usually affected by the disease.

At the age of nine months, without treatment, dopamine levels in the brains of the mouse model were already reduced. This reduction was badociated with the onset of symptoms, including a subtle gait change that mimicked some of the early motor symptoms seen in people with Parkinson's disease, such as "shuffling" of feet during walking. .

When mice were treated for three months with anle138b, starting at nine months, before a significant loss of nerve cells occurred, the researchers observed a reduction in alpha synuclein lumps, restoring levels of dopamine in the brain and protection against death of nerve cells. . This is accompanied by an improvement in the gait of mice, effectively suppressing several Parkinson-like motor symptoms.

These promising results published in Acta Neuropathologica Today, suggest that if anle138b is administered early, before neuronal cell death, it can reduce the dense agglomeration of alpha-synuclein aggregates, potentially blocking Parkinson's disease.

The principal investigator, Professor Maria Grazia Spillantini from the Department of Clinical Neuroscience at the University of Cambridge, said: "Our study shows that by affecting the early aggregation of alpha-synuclein with the molecule anle138b in a new model of transgenic mice, one can rescue dopaminergic dysfunction and typical motor characteristics of Parkinson's disease.

"Using super-resolution microscopy, we could see how the compound works in the mouse brain to achieve this effect." This work paves the way for the development of novel mechanisms-based treatments for Parkinson's disease. and related disorders. "

Dr. Beckie Port, research director at Parkinson UK, said: "The results of this preliminary study are at the basis of our understanding of how syn-alpha-nucleotide is involved in Parkinson's disease and provide new model that could pave the way for future treatments.

"In addition, the discovery that early targeting of aggregation of alpha-synuclein can restore dopamine levels and that rescue cells may prove crucial for stopping Parkinson's disease." in its trajectory.

"Today, we have no treatment that can slow or stop the progression of Parkinson's disease, it is essential to continue to support leading academics, such as those in Cambridge, and to do the same." so that such results are turned into future treatments that we desperately need – the 1 in 37 of us that will be diagnosed in our lives. "

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More information:
"The depopulation of dense alpha-synuclein aggregates is badociated with the rescue of dopaminergic neuron dysfunction and death in a new model of Parkinson's disease", Acta Neuropathologica, 2019.

Provided by
Parkinson's UK