Can a cancer drug prevent memory loss in Alzheimer's disease?

Lead Investigator: Dr Peter Giese

Institution: Institute of Psychiatry, Psychology & Neuroscience - King's College London

Grant Type: Project Grant

Start date: July 2022

Duration: 36 months

Amount: £254,931.00

Project summary

Alzheimer’s disease can cause various changes in the brain that can lead to nerve cells losing their connections with one another. Ultimately causing cells to die, and symptoms of memory loss and dementia. Previous research found that an enzyme, MNK,can disturb protein processes in the brain, causing damage to nerve cell connections.

Dr Giese’s research aims to test whether an anti-cancer drug, eFT508, which blocks the MNK enzyme, can prevent nerve cell damage seen in Alzheimer’s disease. This drug has already been approved for use in treating cancer.

The results from this work might show a potential new treatment for Alzheimer’s disease and form the basis for future clinical trials.

Project background

Despite recent advances in the field, developing new treatments for Alzheimer’s disease is difficult, partly because it is a highly complex disease.

Amyloid is a protein that builds up in the brains of people with Alzheimer’s disease, causing damage. Amyloid build-up can also cause other proteins in the brain to become faulty, disrupting their healthy functions, and leading to loss of connections between nerve cells. As these connections are lost, the nerve cells die, causing the symptoms of dementia. The mechanisms behind these changes in the brain are not well understood.

MNK is an enzyme which helps cells to control how proteins are made. Researchers have shown that faulty MNK enzymes can disrupt the healthy functions of proteins, which is a mechanism of some cancers. A clinically approved, effective anti-cancer drug, called eFT508, is already used as a treatment against faulty MNK enzymes.

Previous research by Dr Giese showed that faulty MNK could also play a role in Alzheimer’s disease, by disrupting the way proteins function in the brain, which can cause nerve cells to lose their connections.

Dr Giese aims to test whether this eFT508 anti-cancer drug could also be used to prevent the loss of nerve cell connections in mice with Alzheimer’s disease.

What does this project involve?

Dr Giese and his team will use cell models of nerve cells to determine whether a cancer drug, eFT508, can prevent the loss of nerve cell connections. The researchers will also use state-of-the-art microscopy to find the most suitable and effective dose of eFT508.

Once the foundations are established, the researchers will determine whether a regular treatment using eFT508 will prevent the loss of connections between nerve cells in mice with Alzheimer’s disease. Dr Giese will examine the mouse brains to look for signs that the treatment is effective and will also perform memory tests to see what impact this treatment may have on dementia symptoms.

By looking closely at the protein mechanisms that are affected by this treatment, Dr Giese also hopes to find early indications of Alzheimer’s disease that could provide new treatment targets to the symptoms of dementia.

How will this project help people with dementia?

This work will determine whether a clinically approved cancer drug could be suitable for preventing memory loss in Alzheimer’s disease. Through this research, Dr Giese hopes to build a foundation for future clinical trials for people with Alzheimer’s disease, bringing them one step closer to effective treatments.

The results of this work will also help researchers to understand the reasons why nerve cells lose their connection in Alzheimer’s disease, contributing to the development of new ideas that aim to develop treatments for the disease.