Existing drug reduces brain shrinkage in mice with Alzheimer’s features

Posted on 27th March 2019

Science translation medicine: A farnesyltransferase inhibitor activates lysozyme and reduces tau pathology in mice with tauopathy

A team of US researchers have found that a drug, lonafarnib, is able to decrease brain shrinkage and reduce the build-up of tau in mice. The findings are published today (Wednesday 27 March) in the journal, Science Translation Medicine.

Tau protein

One of the key hallmark features of Alzheimer’s disease and several other causes of dementia is a build-up of a protein called tau in the brain. In these diseases, tau changes in abnormal ways, which makes the protein behave out-of-character and cause damage in the brain.

There are no drugs available today that stop this abnormal build-up of tau. In this research, scientists in the US looked at the effects of a drug called lonafarnib on mice that had been genetically modified to have a build-up of abnormal tau in the brain.

Using existing drugs

Lonafarnib is a drug that is currently in clinical trials for a number of diseases including cancer. The drug works by interfering with how certain proteins are maintained and removed within cells of the body.

In this study, the researchers used lonafarnib to treat mice bred to have a build-up of tau in their brains. They found that, in high amounts, the drug reduced tau build-up in the mice’s brain after 10 weeks and decreased the amount of brain shrinkage.

They also found high doses of lonafarnib reduced the number of immune cells that were active in the hippocampus – the memory centre of the brain. The drug also improved some of the behavioural problems experienced by the genetically modified mice.

‘A long way from people’

Dr Rosa Sancho, Head of Research from Alzheimer’s Research UK said:

“The diseases that cause dementia are incredibly complex and many biological processes drive their progression. Lonafarnib should be explored as a potential way to target the tau protein, but this early work in mice still has a long way to go before we’ll know whether it could be a medicine that benefits people with dementia.

“Tau is a key player in a number of the diseases that cause dementia and a promising focus for drug discovery efforts worldwide. This study suggests that treatment with lonafarnib may only be effective in the early stages of disease, re-enforcing the importance of research into the early detection of diseases like Alzheimer’s.

“With almost a million people in the UK living with dementia today, we must double efforts towards finding new treatments. The Alzheimer’s Research UK Drug Discovery Alliance is currently working on over 20 promising drug discovery projects, with the goal of bringing new medicines to people with dementia as soon as possible.”

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