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

Lead Investigator: Professor Christian Hölscher

Institution: Lancaster University

Grant type: Drug Discovery project grant

Duration: 24 months

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)

Scientific Title: Novel GLP-1 and GIP dual receptor agonist peptides show neuroprotective effects

What do we already know?

Drugs called 'growth factors' have previously been shown to protect brain cells in several animal models of neurodegenerative disorders. However, these growth factors do not cross the blood- brain-barrier, a barrier that protects the brain from potentially harmful substances in the blood, which limits them as treatment options.

Fortunately, there are some growth factors that can cross the blood-brain-barrier such as insulin and a group of hormones called incretin hormones. 

Recent investigations of the brain cell protection properties of types of incretin hormone, called GLP-1 and GIP, have shown good results in preventing neurodegenerative processes in several mouse models of Alzheimer's disease and also in animal models of Parkinson's disease.

A drug that acts like GLP-1, liraglutide, has shown impressive effects in a mouse models of Alzheimer's disease and in the brains of people with Alzheimer's disease in a biochemical study. 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). 

A recent clinical trial of the older GLP-1 related drug exendin-4 in people with Parkinson's disease has shown impressive results. These researchers have also shown that the hormone GIP protects brain cells in animal models of Alzheimer's disease.

This demonstrates the great potential that drugs that act like incretin hormones have for the protection of brain cells. 

What does this project involve?

New drug development programmes have produced novel drugs that act like both GLP-1 and GIP that have superior properties to drugs that only act as one. Some are already in clinical trials for diabetes and have shown good effects with few side effects in humans. 

In this study, the researchers will test these much improved GLP- 1/GIP dual drugs in mice that show changes similar to those seen in Alzheimer's disease. In addition, they will test drugs that act as another incretin hormone, oxymodulin, which has shown great potential in pilot studies and may be superior to the drugs that act as GLP-1 and GIP. 

All of these novel drugs do not directly affect blood glucose levels and can be given to people that do not have diabetes.

How will this benefit people with dementia?

Treatments available to people with Alzheimer's disease are currently limited. We need to develop better treatments that can benefit more people for longer – however, it can take up to 20 years to develop a drug from scratch.

Our Drug Discovery programme takes drugs that already exist for the treatment of other conditions and develops them further as potential treatments for dementia.

These studies hope to identify treatments for diabetes that show promise in Alzheimer's disease, moving them a stage closer to full-scale clinical trials. 

Using type-2 diabetes drugs like these has already shown promise and one is now in clinical trials for people with early-stage Alzheimer's disease; this study could help us to identify more potential treatments.