Designing drugs to stop overactive immune system in Alzheimer’s disease

Lead Investigator: Dr Wioleta Zelek

Institution: Cardiff University

Grant type: Alzheimer’s Society PhD Studentship

Start date: October 2022

Duration: 36 months

Amount: £85,000.00

“The development of a drug to cross the blood brain barrier that would be able to block… inflammation in the brain is something that needs to be looked into, [especially if] this ultimately leads to a drug treatment for Alzheimer’s”

- Alzheimer’s Society Research Network Volunteer

Project summary

Inflammation in the brain is a defence mechanism against infections and foreign cells. However, excess inflammation can start attacking healthy cells too, which is thought to be a key driver of Alzheimer’s disease. 

Dr Zelek’s research aims to develop new drug treatments which stop this excess inflammation in the brain and prevent healthy brain cells from being attacked. The process of developing these potential drugs could help our understanding of how the disease progresses and would allow researchers to pick the best potential new treatments to take forward into clinical trials for Alzheimer’s disease.

Background

Brain inflammation is one of the major drivers of disease progression in Alzheimer’s disease. Our immune system is armed with a system of proteins in the blood, which tackle bacterial infections either by directly killing bacteria or by stimulating white blood cells to eat them.

Some of these proteins are responsible for directly killing the bacteria and can burst bacterial and human cells by poking holes in their surface. These cells can become leaky, causing inflammation, which can include to excess inflammation in the brain. 

Targeting brain inflammation has been shown as a good approach in other diseases, however for diseases like Alzheimer’s disease there is still progress to be made. 

What does this project involve?

The project will test the idea that stopping specific proteins from poking holes in cells will reduce brain inflammation and prevent degeneration in Alzheimer’s disease. This will be done by generating drugs that can easily cross into the brain to block this activity. 

Antibodies are produced by our immune systems in response to foreign substances, such as viruses or bacteria to remove them from the body. Dr Zelek will be generating specific antibodies    in the lab which can precisely attach to the proteins responsible for directly killing unwanted bacteria . By generating these antibodies, Dr Zelek hopes to understand if new and effective drugs for tackling brain inflammation can be developed. 

How will this project help people with dementia?

The research by Dr Zelek aims to develop new drugs that may be able to target brain inflammation and stop it from killing healthy brain cells. The process of developing these drugs will also help our understanding on how the disease works and give us a better understanding of how to deliver drugs into the brain more easily. The long-term goal of this research is to find the best potential treatments to take into clinical trials for Alzheimer’s disease in the future.