Lixisenatide and Liraglutide: Diabetes Drugs are Potential Alzheimer's Treatments

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A new study, published in Neuropharmacology and conducted by academics at Lancaster University, could bring substantial improvements in the treatment of Alzheimer's disease by using drugs currently on the market to treat type 2 diabetes.

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Alzheimer's disease is the most common cause of dementia; it is predicted there will be more than 520,000 people in the UK with the disease in 2015.

This study shows the newer drug lixisenatide and the older drug liraglutide (which are both currently used in the treatment of type 2 diabetes) have neuroprotective effects (i.e. protect neurons from injury or degeneration) in a mouse model of Alzheimer's disease.

These drugs are more effective than anything currently available for the treatment of this neurodegenerative disease. Furthermore, the drug makers were unaware of the two drugs' incredibly valuable side effects; their neuroprotective qualities.

Professor Christian Hölscher from the Faculty of Health and Medicine is leading the study.

He said: "These are very exciting results. There are no drugs on the market for Alzheimer's disease that actually treat the disease, all we currently have are two types of drugs that mask the symptoms for a while. Lixisenatide and liraglutide offer a real improvement by treating the basis of the disease and, therefore, preventing degeneration."

Professor Hölscher has, with other scientists from Lancaster University, founded the charity Alzheimer's and Parkinson's Trust NorthWest in order fund this research. He adds:

"We urgently need funding to conduct the necessary clinical trials, some of which are currently ongoing. The results of which could bring about a transformation in the treatment of Alzheimer's disease in the very near future, as the drugs we are using in our studies have already been licenced for human use and are on the market."

Background to Alzheimer's disease and how the drugs work:

Impaired insulin has been linked to cerebral degenerative processes in type 2 diabetes and Alzheimer's disease. Insulin desensitisation has also been observed in the Alzheimer's disease brain. The desensitisation could play a role in the development of neurodegenerative disorders as insulin is a growth factor with neuroprotective properties.

Growth factor signalling has been shown to be impaired in the brains of Alzheimer's disease patients. The deletion of the GLP-1 (a growth factor) receptor impairs learning and signal transmission in the brain, therefore treatment with GLP-1 receptor agonists (such as lixisenatide and liraglutide) has the potential to facilitate the repair in the brain and could have beneficial effects in patients with Alzheimer's disease.

The study used APP/PS1 mice, which are transgenic mice that express human genes that cause Alzheimer's. Those genes have been found in people who have a form of Alzheimer's that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated.

As part of the study, researchers observed mice as they carried out a number of memory tasks and recorded neuronal communication in the hippocampus (one of the first areas of the brain to suffer damage in Alzheimer's disease).

This study demonstrated an increase in synaptic numbers in APP/PS1 mice following chronic treatment with GLP-1 receptor agonists (such as lixisenatide or liraglutide). Synapses are of vital importance for communication between neurons and in Alzheimer's disease there is considerable synapse loss. Following chronic drug treatment, it was found that synapse numbers were not only normalised but synapses are kept functioning, ensuring that neurons were still able to communicate information. Furthermore, memory formation is normalised and protected from the detrimental effects of amyloid protein plaques in the brain, which is one of the hallmarks of Alzheimer's disease.

Interestingly, the research also demonstrated that lower doses were just as effective as the higher doses of both drugs administered, suggesting that doses to treat type 2 diabetes may be unnecessarily high to treat neurodegenerative diseases.

Clinical trials using liraglutide are currently taking place; the results of which are expected to be available for review next year. As lixisenatide has proved to be the more successful drug in this study, researchers are currently trying to raise the funds to run clinical trials investigating its effectiveness in the treatment of Alzheimer's disease.

SOURCE:
Lancaster University