How discoveries pave the way for improving people’s lives

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By Aoife Cosgrave | Friday 09 June 2023

Every day, scientists are making new discoveries about how the brain develops, how it works, and how it can go wrong during the many medical conditions that affect this extremely complex organ. There is still however, a lot yet to be explored.

For researchers, a key element of making progress is sharing and collaborating on new ideas and results. Expertise from one particular area of brain research can go on to have an impact on another.

The British Neuroscience Association (BNA) conference gives scientists from across the UK and further afield the opportunity to come together and make new connections.

 

Three people stand behind an Alzheimer's Research UK stall at a conference, holding miniature orange brains.

 

At this year’s conference, ‘the Festival of Neuroscience’, Alzheimer’s Research UK hosted a session on “Developments in Translational Biology” – how new discoveries about the brain and diseases like Alzheimer’s are translated into treatments, diagnosis, and other ways to improve people’s lives.

The event was led by Dr Sara Imarisio, our Head of Strategic Initiatives and provided an opportunity for university and industry scientists to showcase their work.

We heard the latest findings on new drugs to tackle the changes in the brain that cause Alzheimer’s, how using digital tech could detect early signs of dementia, and how researchers are exploring better ways to deliver treatments to the brain.

Can an HIV drug be used to treat Alzheimer’s?

The brain has a special ability to rid itself of toxic or damaged proteins that can build up over time. However, in diseases such as Alzheimer’s, immune cells somehow interfere with the ability of the brain to do this properly. When this happens, toxic proteins build-up and damage nerve cells.

Scientists at the University of Cambridge have been investigating ways to solve this problem. The team are part of the UK Dementia Research Institute, which brings together expert researchers working to improve the lives of people with dementia, and of which Alzheimer’s Research UK is a founding funder and strategic partner.

Prof David Rubinsztein who leads this research group shared the results from their exciting work with a drug that has previously been used to treat HIV, called maraviroc.

Their research involved mice that have been genetically altered to have features of Alzheimer’s, including high levels of toxic tau protein in their brains. The researchers found that in the brains of these mice, immune cells interfere with the ability of the brain to clear away debris in a way that suggested that might be reversible with a drug like maraviroc.

Prof Rubinsztein revealed at the conference that, as they suspected, after treatment with maraviroc, the mice had lower levels of tau. The animals also performed better in a behaviour test, suggesting improvements in learning and memory ability.

While there’s a way to go before researchers know if this same mechanism could be effective in people with Alzheimer’s, unlocking this information and sharing it with the wider research community is vital for scientists to develop drugs that help the brain stay healthy for longer.

Using digital tool kits to detect dementia.

Changes in the brain can happen years before symptoms of Alzheimer’s disease appear.

But getting a diagnosis often takes a long time which is very stressful for people. Early and accurate diagnosis would mean that new drugs could be given to people when changes first start happening.

The digital hub of our Early Detection of Neurodegenerative diseases (EDoN) initiative is focusing on ways in which digital technologies could be harnessed to detect signs of dementia earlier.

At the conference we heard from Dr Giedre Cepukaityte, who’s work involves developing digital toolkits. These include technologies such as wearable monitoring devices that could track changes in the body that previously had not been detected.

There is a window of opportunity between when changes occur in the brain and time of diagnosis of dementia. These tools have the potential to be used at this key timepoint which could allow researchers to identify early warning signs.

Protecting the brain by blocking Notum

Collaboration is key to bridging the gap between new discoveries in the lab and treatments that will one day be used by people living with dementia. Alzheimer Research UK’s Drug Discovery Alliance brings together research and industry experience at the three key sites, including one at University College London.

One of their latest discoveries involves targeting a protein called Notum. Notum regulates a structure in the brain known as the blood-brain barrier. This barrier is made of blood vessel cells, immune cells and nerve cells working together to together to control the brain’s blood supply and to regulate which substances cross it.

Advances in imaging techniques have revealed that the barrier shows signs of damage in people with Alzheimer’s. Deeper investigations have revealed high levels of Notum are at least partly to blame for this.

Dr Stefano Benvegnu is working alongside chemists at the Drug Discovery Institute to find a suitable drug that prevents the activity of Notum, and so restores the normal function of the blood-brain barrier. Pharmacologists came on board to develop experiments to test the performance of the drug.

Dr Benvegnu showed us promising results from their experiments with a drug that blocks Notum’s activity in lab-grown cells from the blood-brain barrier. They are now testing how it performs in a mouse model of Alzheimer’s disease. This takes the research another step towards use in clinical trials.

Getting Alzheimer’s drugs over the blood brain barrier

Once drugs enter the body, they have the difficult journey to get to where they are needed in the brain. One of the challenges is crossing the brain’s own protective barrier.

Scientists at Bicycle Therapeutics have developed small molecules called bicyclic peptides, or ‘Bicycles’ for short – that work in a unique way which allows for a fast, reliable delivery of a drug to the brain.

Dr Inma Rioja, senior vice-president, revealed that their team of researchers began using Bicycles to deliver cancer drugs but have recently expanded into the area of neuroscience. These tiny molecules seem to be perfectly suited get past the layers of protection and make their way into the brain.

This work is in collaboration with other leading pharmaceutical companies and will inform how they develop new treatments for diseases such as Alzheimer’s.

Key take homes

Alzheimer’s is a complex disease, not only do we need to understand what causes it but also how it can be better diagnosed and treated. These researcher talks highlight the huge efforts that are being made to bring expertise from different areas to ultimately make a difference to people with Alzheimer’s and those that care for them.

Not only does Alzheimer’s Research UK facilitate the funding of this important work but by hosting events like this, we’re provide the opportunity to bring researchers together to share and celebrate their progress.

From the BNA we now look to this summer’s Alzheimer’s Association International Conference in Amsterdam – one of the largest dementia research conferences in the world, and where all eyes will be on the announcement of the full set of data from the new Alzheimer’s disease drug, donanemab.

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About the author

Aoife Cosgrave

Science Communications Officer