Collaboration explores alpha-synuclein in disease-modifying therapies

The University of Oxford and Selvita are focused on the process of ubiquitination

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by Andrea Lobo |

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A collaborative effort between the University of Oxford and Selvita will foster the development of potential disease-modifying therapies targeting alpha-synuclein aggregation, a key hallmark of Parkinson’s disease.

The accumulation of toxic aggregates of alpha-synuclein contributes to the progressive loss of dopaminergic neurons, the nerve cells in the brain that produce the signaling molecule dopamine. The consequent decrease in dopamine levels triggers the onset of Parkinson’s disease symptoms.

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Although the disease affects around 7 million people worldwide, so far only therapies that ease motor symptoms by increasing dopamine levels are available. However, they are unable to affect alpha-synuclein aggregation or alter disease progression.

George Tofaris, PhD, and his team at the University of Oxford has identified key protein disposal factors that contribute to alpha-synuclein aggregation, which could be important targets for disease modification, meant to slow disease progression by targeting its underlying cause.

“There is extensive evidence from genetics and pathology implicating alpha-synuclein aggregates as the cause of Parkinson’s. Therefore, promoting the ability of nerve cells to rid themselves of these aggregates is a rational therapeutic strategy in this group of diseases,” Tofaris said in a press release. Tofaris is a professor of neurology and translational neuroscience at Oxford.

In their studies, the team focused particularly on ubiquitination, a process essential to remove unwanted or damaged proteins from cells. They identified several proteins involved in the clearance of alpha-synuclein from neurons, which could be potential targets for Parkinson’s therapies.

The team previously worked with Selvita to develop promising prototype compounds that efficiently promote the clearance of alpha-synuclein aggregates, taking advantage of the company’s experience in the areas of neuroscience and protein degradation.

Seeking improvements

Now, the project aims to further improve the compounds’ pharmacological properties and effectiveness to advance it along the drug discovery pipeline.

“Combination of Selvita’s drug discovery expertise and the world-class innovative research conducted at the University of Oxford, create this exquisite collaboration which holds an immense potential to address the urgent need for disease-modifying treatments to combat Parkinson’s disease,” said Edyta Jaworska, vice president sales, drug discovery Europe and Asia at Selvita.

Selvita is a European preclinical contract research organization that offers comprehensive services from early drug discovery to preclinical drug development.