Parkinson’s UK, University of Sheffield to develop new Parkinson’s drug

Parkinson's UK, the largest charitable funder of Parkinson's research in Europe, is investing up to £1.2 million into a pioneering one-year project in partnership with the University of Sheffield.

The project aims to refine a molecule that could be developed into a drug to protect dopamine-producing brain cells and slow down the progression of Parkinson's.

The funding boost comes via the charity's Parkinson's Virtual Biotech initiative, which is plugging the funding gap in drug development and fast-tracking the development of new treatments for people with Parkinson's.

Scientists at the University of Sheffield's Institute of Translational Neuroscience (SITraN) and Parkinson's UK have been developing molecules that can boost the function of the brain's energy-producing mitochondria, to halt Parkinson's - something no treatment can currently do.

Dopamine is a chemical which allows messages to be sent to the parts of the brain that help to coordinate movement. To do this effectively, the dopamine-producing brain cells need to be constantly active and they rely on mitochondria to function properly. Any disruption could lead to dysfunction and degeneration of the brain cells and eventual cell death. Parkinson's is what happens when those cells die.

Earlier work funded by a Parkinson's UK Senior Fellowship grant and given to Dr Heather Mortiboys at the University of Sheffield, identified two molecules with excellent mitochondrial restoration properties.

The project continued with funding through the Virtual Biotech and saw Dr Mortiboys work closely with Parkinson's UK Drug Discovery experts.

Together they made modifications to these molecules which maximized their ability to boost the mitochondria without causing side effects. In a mould-breaking approach to drug discovery, scientists have been using cells from people with Parkinson's and will continue to test molecules in these cells throughout and into the next phase of the project.

The new project will bring together biology and chemistry experts from the University of Sheffield, Parkinson's UK and world leading contract research organizations to further develop the modified molecules. This innovative team will investigate how the molecules work and what protein(s) they interact with inside brain cells.

This next stage of the project aims to develop a drug-like molecule with good efficacy in cellular models of Parkinson's. This would then allow future work to take place to assess the effectiveness of this approach in animal models before moving into clinical trials in people with Parkinson's.

Dr Arthur Roach, Director of Research at Parkinson's UK, said:

"We're excited to fund the next stage of this full scale project combining our own drug discovery know-how with experts from the University of Sheffield and two world-leading contract research organizations.

Looking back, it's incredible to see how this project had its origin in a small academic grant from Parkinson's UK to screen for molecules that rescue defective mitochondria inside neurons. Since then, the charity and university have continued to work closely together to improve those initial compounds.

"This new funding will greatly accelerate the project and shows our commitment to working with ground-breaking academic researchers in the UK and taking their discoveries from the lab towards clinical trials. With 145,000 people living with Parkinson's in the UK, there is a desperate need for new and better treatments and we hope this project will one day deliver a life-changing drug for people living with the condition."

We're delighted to continue our work with Parkinson's UK to refine these promising molecules to develop a treatment that could stop Parkinson's in its tracks. The team has identified not only molecules which can restore mitochondrial function in dopaminergic neurons from people with Parkinson's, but also a novel mechanism by which they do this."

Dr Heather Mortiboys, Senior Lecturer, Institute of Translational Neuroscience, University of Sheffield

"We're progressing both a novel mitochondrial therapeutic target and novel molecules which act upon this target. The aim is to have a lead molecule which is active at the mitochondrial target, can restore mitochondrial function in dopaminergic neurons derived from people with Parkinson's and is able to get into the brain in a whole organism."

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