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Existing drugs step up in battle against neurodegenerative disease

Research published today in the journal ‘Brain’ shows that two existing drugs can block the death of brain cells in mice with neurodegenerative disease.


 

Scientists led by Prof Giovanna Mallucci at the University of Cambridge have demonstrated that trazodone, a licensed antidepressant, and ‘DBM’, a compound found in liquorice that is being tested in cancer, both stave off the demise of mouse brain cells by acting on a natural defence mechanism called the ‘unfolded protein response’.

Many neurodegenerative diseases, including PSP, CBD and frontotemporal dementia, are characterized by the build up of tangled, or ‘misfolded’, proteins such as tau. The unfolded protein response is the body’s attempt to deal with this by suspending protein production in the cell. However, the over-activation of this response in neurodegenerative disease may eventually lead to complete cell shut down and cell death.

Prof Mallucci’s team screened many hundreds of existing drugs in the lab for their ability to reduce the unfolded protein response. They then went on to test trazodone and DBM in mice with gene mutations leading to the animal form of frontotemporal dementia associated with tau accumulation. The drugs prevented the death of brain cells and the mice also improved in memory tests.

Prof James Rowe, a member of the team running PSPA’s PROSPECT study and a colleague of Prof Mallucci’s at Cambridge, said: “This is a very exciting breakthrough. There is still some way to go to show this is safe and effective in people with PSP, rather than mice, and to know when to treat people and at what dose. But, PSP is an ideal condition to test these drugs and we need a thorough clinical trial to establish whether they are of benefit for patients.”

Prof Rowe also added a note of caution: “Even though trazodone is widely used in psychiatry and occasionally for symptom relief in PSP, it is not without side effects, including drowsiness and possibly some increased risk of falls, so I would recommend that it only be used under specialised supervision where clinically necessary or in a clinical trial.”

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