Mice are vital in the search for effective new dementia treatments
Cambridge researchers are leading drug discovery to develop safer, more effective treatments for the millions of people affected by Alzheimer’s and other neurodegenerative diseases.
According to Alzheimer’s Research UK, if nothing changes one in two of us will be affected by dementia in our lifetime, either by caring for someone with the condition, developing it ourselves, or worse, both. David Harrison is no exception: his mother was diagnosed with Alzheimer’s disease several years ago – and he sees the effects of dementia on a regular basis.
“There are many devastating neurodegenerative conditions that we just haven’t got effective ways to treat,” he says, adding:
"So many people develop Alzheimer’s and Parkinson’s disease - everybody knows somebody who’s affected."
In the last few years, new drugs have come onto the market for Alzheimer’s disease that can slow the rate of cognitive decline - but they don’t work for everybody, can have serious side effects, and their insufficient cost effectiveness has prevented healthcare adoption in the NHS.
Harrison says many pharmaceutical companies have lost confidence in working in this area because the risk of failure is too great.
“In the past, drug companies put a lot of money and effort into finding treatments for dementia,” he says, “but we’re talking about a range of really complex diseases and there’s been a high, and costly, failure rate in clinical trials and drug development. While there are new drugs coming out, which offer great hope for patients, they're not ideal and we need to find better ones.”
This is where ‘academic drug discovery’ steps in. With professional and personal motivations driving him, Harrison - a senior researcher at Cambridge’s ALBORADA Drug Discovery Institute – is part of a team dedicated to finding new dementia medicines. The Institute is part of the University of Cambridge, funded by Alzheimer’s Research UK, and based on the Cambridge Biomedical Campus.
"Dementia has often been viewed as something that happens normally as people age, but it's not. It's a disease that we need to treat, so that people can live well and stay independent in later life."
David Harrison, senior researcher at Cambridge’s ALBORADA Drug Discovery Institute
An academic approach to drug discovery
Many research groups are working to identify potential new drug targets that could lead to better treatments for dementia. The aim of the ALBORADA Drug Discovery Institute is to develop these ideas to the point where pharmaceutical partners can then more confidently take things forward.
That point is when a new drug molecule is proven to effectively treat the hallmarks of dementia in an animal model of the disease.
With expertise in drug discovery, the team is designing and making chemical molecules - the basis of future drugs - and testing whether they work on novel targets in the body. Harrison says:
"The effectiveness of any drug depends on its ability to interact with the right target in the body.
We’re building on Cambridge’s world-leading research expertise into the biology behind dementia, and aiming to validate promising new drug targets."
“Alzheimer's disease, and other neurodegenerative diseases like Parkinson's and Huntington's, all involve the formation of aggregates of misfolded proteins that spread throughout the brain - causing brain cells to stop functioning properly and die, which results in the dementia symptoms we’re familiar with like memory loss and behaviour change,” says Harrison.
“The new drugs that have come out recently remove beta amyloid - one of these misfolded proteins - which is found in the brains of people affected by Alzheimer’s disease. They don’t work for everybody, but their discovery has given us added confidence that other treatments can be found. We’re looking for different ways of treating neurodegenerative disease."
Two principal approaches are being explored by the ALBORADA Drug Discovery Institute. The first is to harness the cells’ own mechanisms to break down and remove misfolded proteins before they cause irreparable damage to nerve cells and their connections in the brain. The second is to reduce the damaging inflammation these misfolded proteins cause in the brain.
Together, the interventions could halt neurodegenerative disease before the debilitating effects take hold.
"Our approach is based on the fact there are common mechanisms in play across many of these diseases: we want to find common ways to treat them as well."
David Harrison
How animals can help in testing new treatments
Before any new drug can go into human clinical trials with the aim of being approved for human use, it must be tested for efficacy and safety as thoroughly as possible.
One approach being used by the team is to give mice a drug that causes inflammation in the brain, to model what happens in neurodegenerative disease. The inflammation is too low-level to cause symptoms, but molecular changes in the brain can be detected - and these changes can then be reversed using molecules developed by the Institute’s chemists.
The mouse brains are then removed so the team can assess these inflammatory changes - either by measuring the expression of key inflammatory genes, or by slicing the brains and looking at the changes under a microscope. This allows the team to select the molecules which show the best activity, for further development.
“We’re really excited to have developed a mouse model that represents a key feature of many neurodegenerative diseases,” says Harrison, adding: “the brain is such a complex organ that it’s very difficult to model outside a live animal.”
While the team uses test-tube and computer-based models routinely as part of its work, animal models are vital in understanding how the many different cell types in the brain interact together in disease.
They are also vital in understanding how potential drugs are metabolised and distributed throughout the body, and in looking for any adverse effects that may occur in other tissues.
“We need to test on whole brains because they’re complex. We also need to understand how the whole body is affected by the drug, to work out the right dosage and look for side-effects,” says Harrison.
The University only allows research using animals when it is considered necessary and justified, and reviews work regularly to ensure that the researchers treat all animals humanely and use as few of them as possible.
Even when the researchers find that potential drugs have no effect, the mice have played an important role. The team publishes negative results so others working in the field don’t try the same thing. Successful results, on the other hand, are presented to pharmaceutical companies as partnership opportunities for further development.
Harrison says: “Almost one million people are estimated to be living with dementia in the UK. We need to find better treatment options for them, and for future sufferers."
This cross section of a mouse brain shows where changes in gene expression occur (in yellow) following treatment with a therapeutic drug.
This cross section of a mouse brain shows where changes in gene expression occur (in yellow) following treatment with a therapeutic drug.
A highly magnified image of the mouse hippocampus - a brain region known to be affected in neurodegenerative diseases. The brain has a defensive barrier that stops toxins entering, but this can stop drugs too. The team uses a non-reproducing virus, injected into the veins and labelled with a green fluorescent protein, to carry drugs across the barrier.
A highly magnified image of the mouse hippocampus - a brain region known to be affected in neurodegenerative diseases. The brain has a defensive barrier that stops toxins entering, but this can stop drugs too. The team uses a non-reproducing virus, injected into the veins and labelled with a green fluorescent protein, to carry drugs across the barrier.
"The animals we use are an essential part of the drug discovery process - they could help us change people’s lives.”
Published 30 July, 2025
Image of black mouse (top): anyaivanova/ Getty
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