A DISCOVERY by scientists in Dundee could pave the way to new treatments for neuro-degenerative disorders such as motor neurone disease, Parkinson’s and multiple sclerosis.
They believe they have unravelled the “unique” workings of an enzyme which drives axons - the nerve fibres which carry electrical impulses - to self-destruct.
As nerve injury occurs in the early stages of many neurodegenerative diseases, developing drugs to block this enzyme could offer a way to halt their progress.
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The research was led by Dr Satpal Virdee at Dundee University’s Virdee Lab, in collaboration with colleagues at Cambridge University.
“There is huge unmet clinical need for neurodegenerative diseases and neurological disorders and there is also no way of limiting the nerve damage often associated with the administration of cancer drugs,” said Dr Virdee.
“Unfortunately, there has been a paucity of enzymes that have been experimentally validated as promising drug targets.”
Former Scotland rugby star Doddie Weir and late political campaigner Gordon Aikman have raised awareness of MND in particular through their own battles with the disease.
Scotland also has one of the world's highest rates of multiple sclerosis (MS).
The latest developments come after scientists at the Virdee Lab first discovered unusual structures on the enzyme, known as MYCBP2, in 2018.
Other studies have shown that if this enzyme is removed from animals, it has a neuro-protective effect.
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The new study sought to understand the molecular triggers which set off the enzyme.
“Blocking an enzyme’s activity with a small molecule drug is a tried and tested strategy for treating disease,” said Dr Virdee.
“A problem with neurodegenerative diseases is that very few enzymes whose activity drives the degenerative process have been identified.
“Furthermore, the features of an enzyme that successfully engage a drug molecule are often shared by related enzymes.
"This makes it extremely challenging to develop specific drugs and is one of the reasons why many drugs have undesirable side effects.
“This study provides structural and molecular detail on the mechanism of MYCBP2 enzyme activity, while the seemingly unique mechanism of MYCBP2 should greatly facilitate the development of drugs that are highly specific against it.”
The findings are published today in Nature Chemical Biology.
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