Testing type-2 diabetes drugs as potential treatments for Alzheimer's disease

Read about a research project we funded: Novel GLP-1 and GIP dual receptor agonist peptides show neuroprotective effects.

Lead Investigator: Professor Christian Holscher

  • Institution: Lancaster University
  • Grant type: 
  • Grant amount: $248,000 (this project amount is in dollars as it was awarded as part of a joint funding call with the Alzheimer's Drug Discovery Foundation - Alzheimer's Society are funding half of this amount)
  • Start date: Jan 2015
  • Completion date: Jan 2017

What did the researchers do?

Changing the levels of particular hormones in the brain, called Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and Glucagon (Gcg), have shown good results in preventing neurodegeneration in several mouse models of Alzheimer's disease. 

These hormones are involved in the development of type 2 diabetes. Trials of drugs developed to target these hormones in order to treat type 2 diabetes have also shown positive effects on brain cells. Repurposing of current drugs already on the market can make getting treatments to patients a lot quicker and easier.

A drug that acts like GLP-1, liraglutide, has shown impressive effects in mouse models of Alzheimer's disease and in the brains of people with Alzheimer's disease. Based on these findings, a clinical trial of liraglutide in people with early-stage Alzheimer's disease is under way (this trial is also part of our Drug Discovery programme). 

New drug development programmes have produced drugs that act like both GLP-1 and GIP. Targeting two or more of these hormones at once has proven to be more effective than separate drugs. Some are already in clinical trials for diabetes and have shown good effects with few side effects in humans. 

In this study, the researchers tested these much improved combination drugs in mice that show changes similar to those seen in Alzheimer's disease. 

What were the key results, and how will this help in the fight against dementia?

The researchers tested both a double (GLP-1/GIP) and triple (GLP-1/GIP/Gcg) target drug. In the Alzheimer’s disease mouse models both drugs showed clear improvements in memory formation measured using behavioural tests. They also showed higher activity of the cells in the brain that are responsible for forming memory. 

Treatment with the drugs reduced the two key markers of Alzheimer’s disease. Levels of the amyloid and tau protein that characterise the disease were reduced after drug treatment. 

These results further strengthen the case for the targeting of these hormones in the brain of people with Alzheimer’s disease. It also demonstrates the importance of investigating current drugs for new uses, as this could allow these treatments to be brought to market sooner. Identifying targets for reducing the effects of Alzheimer’s disease is key in the development of better and more effective treatments. 

What happened next? Future work and additional grants

Further testing of these drugs to identify the most appropriate doses is needed.

The researchers have also identified a further two drugs that are able to cross into the brain more quickly than the ones in this study. These will also be tested in mouse models of Alzheimer’s disease.

The team will be applying for further funding to carry out this work.  

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