Lead Investigator: Dr David Brough
Institution: University of Manchester
Grant type: PhD studentship
Duration: 36 months
Scientific Title: Identifying a new drug target for the treatment of Alzheimer's disease
Why did we fund this project?
Comments from members of our Research Network:
"I think this research, targeting inflammation, is an important area and the possibility of re-purposing existing drugs is particularly welcome."
"There is a strong sense of community running through this proposal. A lot of work has already been done on the effects of inflammation on Alzheimer's Disease. This appears to take it to the next step."
"The search for therapeutic targets for the treatment of AD is welcome to members of the AS Research Network and the wider AD community. The research planned in this proposal seems to offer potential in this direction."
What do we already know?
Inflammation occurs when the body's immune system fights an infection or injury. However, evidence indicates that too much inflammation is damaging and may have a role in the development of Alzheimer's disease.
Many of the proteins that are associated with inflammation can join together in the brain and work together to help to fight the cause of injury or infection. These joined-up proteins are collectively known as the 'inflammasome'. Recent research indicates that the inflammasome can worsen the damage caused to the brain in Alzheimer's disease.
What does this project involve?
The team are focusing on a particular protein, called VRAC, which controls the inflammasome. Previous work by this group indicates that this protein could be a good potential target for the treatment of Alzheimer's disease. They found that an existing class of drugs, called fenamate NSAIDS, can target VRAC and this can reduce inflammation and help to improve memory problems in mice. However, fenamate NSAIDS can cause side effects. Therefore the researchers are aiming to find out if there are other drugs that can be developed that target VRAC without causing these side effects.
The PhD student will first use a computer programme to identify potential drugs that could target the VRAC protein without causing side effects. They will test the most promising drugs on cells grown in the lab to find out whether they are effective in preventing inflammation. Those that pass this stage will then be tested in mice, to make sure that they can also have an effect on the inflammasome in a living animal. Finally, they will see if targeting the inflammasome using these drugs can have an effect on the memories of mice showing symptoms of Alzheimer's disease.
How will this benefit people with dementia?
There have been no new treatments for Alzheimer's disease in over a decade. A key area of research is finding new targets for the development of potential treatments. This research aims to find out whether targeting the inflammasome can be an effective way of preventing or slowing down the symptoms of Alzheimer's disease in animals. If successful, the team hope to test the drugs that they find in clinical trials involving people.