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Treating brain diseases like Alzheimer’s and Parkinson’s ‘step closer’ thanks to Manchester uni breakthrough

By Danielle Wainwright

Degenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s may soon be treatable thanks to a significant breakthrough by scientists at The University of Manchester.

Neurodegenerative diseases such as these affect 37million people globally and the research hopes to dramatically reduce the number of sufferers by 2030.

Researchers at the Manchester Institute of Biotechnology have detailed how an enzyme in the brain interacts with a drug-like lead compound (UPF 648) for Huntington’s disease to inhibit its activity which can be developed as an effective treatment for neurodegenerative diseases.

Cath Stanley, chief executive of the Huntington’s Disease Association, said: “This research is a really exciting piece of the jigsaw that enables us to understand a little more and takes us a step closer to being able to provide an effective treatment for Huntington’s Disease.”

Researchers from the University of Leicester and the University of Lisbon were also involved and were the first to identify the molecular structure of the enzyme kynurenine 3-monooxygense (KMO), which is found in the human brain.

The scientists then studied how UPF 648 binds incredibly tightly to enzyme KMO to act as an inhibitor. Previous studies with animal models of neurodegenerative disease have showed that switching off the KMO activity through drug binding should be effective in the treatment of brain disorders.

Professor Nigel Scrutton, who led the study, said: “UPF 648 works very well as an inhibitor of enzyme activity. However, in its current form it does not pass into the brain from the blood. The search is now on for related compounds that can both inhibit the enzyme and pass into the brain.

“Our research detailing the molecular structure of the enzyme now enables a search for new KMO inhibitors that are able to cross the blood-brain barrier.

“This provides real hope for developing drug therapies to target neurodegenerative diseases such as Huntington’s, Alzheimer’s and Parkinson’s diseases.”

Professor Sarah Tabrizi, head of the Huntington’s disease research team at University College London’s Institute for Neurology, said: “Unlocking the crystal structure of KMO is a real boost to our efforts to find treatments for this devastating disease.

“It provides a solid basis for the optimisation of inhibitor drugs like UPF 648 that are being developed by the global Huntington’s disease research community.”

For more information about neurodegenerative disease please visit the Neurodegenerative Disease Research website at www.neurodegenerationresearch.eu

Picture courtesy of EMSL, with thanks.

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