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New drug compound targeting Alzheimer's protein identified

Posted on 10/05/2018

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Using an experimental drug called Compound 43, King’s College London researchers have identified a promising approach for tackling the hallmark Alzheimer’s disease protein, tau. The findings of the research are published today in Acta Neuropathologica Communications.

One of the key features of Alzheimer’s is an abnormal build-up of a protein called tau in the brain, but there are several different neurodegenerative diseases that are caused by abnormal tau. Known collectively as tauopathies, these diseases affect hundreds of thousands of people in the UK.

In healthy nerve cells, tau protein plays an important role supporting the structure of the cell. In diseases like Alzheimer’s, tau becomes overloaded with chemical tags called phosphates, and strands of the protein stick together to form toxic tangles.

In this study, Dr Jonathan Morris from the Faculty of Life Sciences & Medicine and Professor Diane Hanger from the Institute of Psychiatry, Psychology & Neuroscience, focused on molecules called thousand and one amino acid kinases or TAOKs. TAOKs number among several proteins that can regulate chemical reactions in which tau gets tagged with phosphates. The team set out to investigate whether TAOKs might be involved with the abnormal addition of phosphate tags that scientists see in diseases like Alzheimer’s.

The researchers analysed brain tissues collected by the MRC London Neurodegenerative Disease Brain Bank, from people who died with either Alzheimer’s disease or frontotemporal dementia – two forms of dementia that involve the build-up of tau. They found evidence of abnormal TAOK activity alongside tau tangles in both cases, implicating these proteins in driving damaging disease processes.

The researchers studied the effect of blocking TAOK activity in nerve cells grown in the laboratory. Using stem cell techniques, they were able to grow human nerve cells that reproduced the processes that cause tauopathies in people. Using an experimental drug called Compound 43, the team reduced the activity of TAOK in cells and successfully lowered the amount of abnormal tau that the cells produced.

Dr Jonathan Morris, who has previously pioneered research into the role of TAOKs in the development of cancer, said:

‘Tau is a key player in a number of diseases that cause dementia, and an important target for future dementia treatments. These findings are at an early stage of development but highlight a potential new approach for tackling the build-up of tau and limiting the damage to nerve cells, which causes the devastating symptoms of dementia.

‘We are now working with experts from the Alzheimer’s Research UK’s Oxford Drug Discovery Institute to further assess the potential of targeting TAOKs to treat diseases like Alzheimer’s, and to develop this work towards something that could help people with dementia.’

The study was funded by Alzheimer’s Research UK.

 

Paper reference 

'A new TAO kinase inhibitor reduces tau phosphorylation at sites associated with neurodegeneration in human tauopathies' by Giacomini et al, Acta Neuropathologica Communications, DOI: 10.1186/s40478-018-0539-8

 

Contact 

For further media information please contact Robin Bisson, Senior Press Officer, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, robin.bisson@kcl.ac.uk / +44 20 7848 5377 / +44 7718 697176.

 

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