brainscanFaculty scientists have taken a significant step towards developing an effective treatment for neurodegenerative diseases such as Huntington’s, Alzheimer’s, and Parkinson’s. Manchester Institute of Biotechnology researchers have detailed how an enzyme in the brain interacts with a drug-like lead compound for Huntington’s, inhibiting its activity. Their findings demonstrate that this can be developed as an effective treatment for these difficult to treat conditions.

Working with colleagues at the Universities of Leicester and Lisbon, the researchers identified the molecular structure of the enzyme kynurenine 3-monooxygense (KMO), found in the human brain. This is the first time the crystal structure of KMO has been established, and the process took five years to complete.

The scientists then studied how the compound UPF 648 binds incredibly tightly to the enzyme, acting as an inhibitor. Previous studies had shown that switching off the enzyme activity through drug binding should be effective when treating brain disorders. Professor Nigel Scrutton, who led the study, said:

“UPF 648 works effectively as an enzyme activity inhibitor. However, in its current form it doesn’t pass from the blood into the brain. Our research enables a search for new KMO inhibitors that are able to cross the blood-brain barrier. This provides real hope for developing drug therapies for diseases such as Huntington’s, Alzheimer’s, and Parkinson’s. ”

Dr Flaviano Giorgini from the University of Leicester said:

“This is a big move forward for the development of KMO inhibiting drugs. It is hoped that such compounds may ultimately be tested in clinical trials and prove beneficial for patients.”

Cath Stanley, Chief Executive of the Huntington’s Disease Association, welcomed the findings:

“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”

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