Why a diabetes drug may offer potential treatment for Alzheimer’s disease


By Ally Matthews | Tuesday 28 April 2015

You may have seen in the news recently the announcement that a drug commonly used to treat type 2 diabetes is to be tested in a clinical trial for Alzheimer’s disease. The study led by scientists at Imperial College London will investigate the drug, liraglutide, in a phase II trial of people with mild Alzheimer’s disease at medical centres across the UK. Let’s take a look at why a diabetes drug is being tested in people with Alzheimer’s.

So what do we know about a link between type 2 diabetes and Alzheimer’s disease?

Type 2 diabetes is a disease which is characterised by high levels of blood glucose. The hormone insulin plays an important role in controlling blood glucose levels. Specifically, insulin acts as a messenger to instruct the cells in the body to take up glucose from the blood, so that it can be used for energy. Type 2 diabetes occurs when the pancreas does not produce enough insulin for effective biological function, or when the cells in the body do not ‘react’ to insulin.

The chain of events that are triggered by insulin are important for keeping the brain active and healthy, and include protecting against nerve cell death, as well as nerve cell growth and repair. Previous studies suggest that treating people with insulin leads to an improvement in memory and cognitive abilities. It seems that people with Alzheimer’s disease have ‘resistance’ to the chain of events triggered by insulin and we now know that type 2 diabetes can increase the risk of dementia. Clearly there is a lot of interest in the link between diabetes and Alzheimer’s disease. Stopping the damage caused by Alzheimer’s disease is a huge ask, but we urgently need to find new treatments. Using ‘repurposed’ drugs may be a possibility.

Building on earlier work

A team of scientists led by Prof Christian Holscher at Lancaster University have been investigating the link between disrupted insulin signalling and Alzheimer’s, benefitting in the past from funding through Alzheimer’s Research UK. More recently, they have investigated the effect of liraglutide – a drug licensed for treatment of type 2 diabetes – in mice with some of the hallmark features of Alzheimer’s disease, as well as in healthy mice. Liraglutide has a similar shape and structure to a hormone that acts to stimulate insulin production. As part of the study, the researchers observed mice treated either with or without the drug as they carried out a number of memory tasks. They found that liraglutide improved the performance and learning abilities of mice with features of Alzheimer’s compared to those treated with a placebo – an inactive drug. The team used a variety of molecular approaches to try to understand how liraglutide prevented memory impairment. They showed that there was a reduction in amyloid – a toxic protein that builds-up in the brain in Alzheimer’s disease – in liraglutide-treated mice. However, positive results from animal studies – a vital first step in research – do not always translate into benefits for people.

The clinical trial

Clinical trials are crucial to understand whether a treatment could help people with Alzheimer’s disease. And that is exactly what scientists are now trying to do with Liraglutide. Scientists at Imperial College London are recruiting over 200 people with mild Alzheimer’s disease, to a year-long trial to test the effects of liraglutide. This study will take place across several medical centres across the UK, including King’s College London, Cambridge, Oxford, Birmingham, Bristol, Brighton and Southampton.

Click to enlarge

Click to enlarge

The researchers will randomise the participants into two groups to receive either liraglutide, or a placebo. The brain will be scanned at the start of the trial and after 12 months to see if there are any changes in how glucose is used in the brain cells, inflammation, the structure of the brain and brain volume between the two groups. Participants will also take cognitive tests to see if liraglutide has an effect on memory and thinking functions. This will help the researchers to understand how the drug acts on the brain during the disease.

As liraglutide is currently licensed for treatment of type 2 diabetes, it has already passed through large parts of the drug development process. Repurposing drugs that were originally developed to treat other diseases makes it cheaper and faster to develop new treatments for Alzheimer’s disease than would be the case for developing new drugs. Our Global Clinical Trials Fund will invest in both new and repurposed drugs to help accelerate progress towards patient benefit.

What does this mean for me?

It is a long road from a promising idea in the lab to treatment in the clinic, and we won’t know whether liraglutide holds potential for people with Alzheimer’s disease until this clinical trial study has been completed and the results analysed. However, in order for trials like this, and many others like them, we need your help. If you would like to take part in clinical research, you can sign-up to ‘Join Dementia Research’ a new scheme to get more people involved in vital studies taking place up and down the country. You can read more on the website or give us a call on 0300 1115111.

For the best chance of success, we need to see many different approaches tested, which is why Alzheimer’s Research UK is investing in initiatives such as the Dementia Consortium and the Global Clinical Trials Fund. We have also launched a Drug Discovery Alliance, a network of three drug discovery institutes that are the first of their kind in the UK. These initiatives will support researchers to find new treatments for Alzheimer’s disease and other causes of dementia to help the 850,000 people in this country living with the condition.

Visit our award-winning dementia lab to find out more about research into dementia.

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Ally Matthews

Team: Science news