Researchers design ‘switch’ that could slow Parkinson’s progress

Scientists have developed a molecule that prevents toxic protein clumping in Parkinson’s disease, demonstrating its effect in an animal model.

Researchers at the University of Bath, working with the Universities of Oxford and Bristol, engineered a peptide fragment that locks alpha-synuclein – a protein that forms toxic clumps in Parkinson’s – into its healthy shape, blocking the deposits that kill nerve cells.

The team showed the peptide is stable, can enter brain-like cells, and restored movement while reducing protein deposits in a worm model of Parkinson’s.

Professor Jody Mason, from the Department of Life Sciences at the University of Bath, said: “Our work shows that it is possible to rationally design small peptides that not only prevent harmful protein aggregation but also function inside living systems.

“This opens an exciting path towards new therapies for Parkinson’s and related diseases, where treatment options remain extremely limited.”

Alpha-synuclein is a protein mainly found in brain cells (neurons) where it regulates the release of neurotransmitters such as dopamine, allowing communication between neurons.

In Parkinson’s disease, the protein clumps together in toxic deposits that cause nerve cell death.

This leads to symptoms including tremors, stiffness and difficulty moving. While treatments can ease symptoms, there is currently no cure.

Normally, alpha-synuclein’s natural state is like a flexible strand, but when active it coils into a helix – a spiral structure critical for binding and moving parcels of dopamine.

The engineered peptide – a short protein fragment – locks alpha-synuclein into this healthy form, preventing it from turning into harmful clumps.

Laboratory tests showed the peptide could enter brain-like cells and restore movement in the animal model.

This breakthrough demonstrates the potential of rational peptide design to transform large, unstable proteins into compact, drug-like molecules.

The findings mark what researchers describe as a significant step towards developing new peptide-based treatments for currently untreatable neurodegenerative conditions.

Dr Julia Dudley, head of research at Alzheimer’s Research UK, which funded the research, said: “Dementia isn’t an inevitable part of ageing; it’s caused by diseases like Alzheimer’s.

“To make progress towards a cure for all forms of dementia, we need research focused on developing a broad range of treatments that can slow, stop and ultimately reverse these diseases.

“Although this is early research in an animal model, it’s exciting to see that this new molecule can prevent the build-up of misfolded alpha-synuclein.

“By stabilising alpha-synuclein in its healthy form, this could open the door to a new class of treatments that could slow progression in diseases like Parkinson’s and dementia with Lewy bodies.

“We look forward to seeing this research taken to the next stage, potentially exploring how it would work in people.”