Conditions such as Alzheimer’s and Parkinson’s that first affect the brain before attacking other crucial body systems are difficult to stop – and many new drugs have failed to fulfil their promise.
Parkinson’s is a progressive neurodegenerative disorder affecting more than 10 million people worldwide with no cure available and current treatment limited to symptomatic management.
But researchers at the University of Dundee have discovered a molecule that helps to eliminate a Parkinson’s disease-causing protein.
Dundee University is one of the world leaders in TPD (targeted protein degradation), a field of research that’s revolutionising drug discovery and which has received billions of pounds of investment in recent years.
This approach is making the treatment of diseases previously thought to be untreatable a reality.
Targeted protein degradation co-opts the cell’s natural disposal systems to remove disease-causing proteins.
The approach would work in conditions including cancer, inflammation, dermatology, immunology and respiratory diseases.
Researchers from the University’s Centre for Targeted Protein Degradation (CeTPD) and collaborating MRC Unit (MRC-PPU) have made significant strides towards developing new therapies originating from the molecule XL01126.
It completely destroys a protein known to play a key role in the development of Parkinson’s by using the cell’s own waste disposal system.
The research also demonstrates that XL01126 can be taken by mouth and passes the blood-brain barrier, which can be difficult to achieve.
The Dundee team, led by Dr Xingui Liu and Dr Alexia Kalogeropulou, believe XL01126 will be a very useful research tool and has the potential to generate treatments for Parkinson’s.
XL01126 moves the field of targeted protein degradation one step closer to developing drugs against neurodegenerative diseases.
The next steps in developing treatments are currently underway with pre-clinical studies to establish safety and effectiveness.
Dundee researchers and teams led by CeTPD director Professor Alessio Ciulli have previously revealed fundamental insights into the working of the degrader molecules they have designed and which are used across the globe.
Moreover, the seminal work conducted by the lab of MRC-PPU director Professor Dario Alessi has been instrumental in identifying the best degraders.
Degrading (destroying) rather than inhibiting a target protein has several advantages such as a stronger drug response at lower doses, a more targeted intervention with potentially reduced side effects and disease resistance.
This ingenious Dundee approach of finding degraders for toxic molecules could produce medicines that work against many more diseases.