Taking an innovative approach to designing potential treatments for Alzheimer’s disease

Lead Investigator: Dr Francesco Antonio Aprile 
Institution: University of Cambridge
Grant type: Senior Fellowship
Duration: 48 months
Amount: £399,970
Scientific Title: Rational Design of Anti-Aggregation Antibodies against Alzheimer's Disease

 Why did we fund this project?

Comments from members of our Research Network:

'The attempt to design antibodies in the fight against Alzheimer's disease is a novel approach, and if successful would be welcomed by all concerned.'

'A well written project ... I feel he deserves the funding.'

'Strong team and convincing research proposal.' 

What do we already know?

One of the hallmarks of Alzheimer's disease is toxic clumps of a protein known as amyloid. These amyloid build ups are thought to cause damage to brain cells, leading to disease symptoms such as memory loss.

Targeting the amyloid protein is one of the main approaches researchers have taken when developing potential drugs for the treatment of Alzheimer's disease. One way to target particular proteins is through the use of a type of treatment called antibodies. Antibody treatments are being used more frequently in medicine, for example in the treatment of some cancers. 

Most antibody treatments aim to harness the immune system to tackle the causes of the condition. However, this approach has produced disappointing results so far in trials of potential treatments for Alzheimer's disease, including a recent high profile failure of the antibody drug solanezumab..
Dr Aprile believes that rather than using antibodies to target the immune system, they could instead be used directly target the amyloid protein. These antibodies could then be used to prevent amyloid from forming harmful build ups in the brain. 

What does this project involve?

Dr Aprile will use a computer programme to design special antibodies to prevent the amyloid protein from forming toxic build ups. The antibodies that look most promising will then be tested in a laboratory setting, including using the worm C. elegans to understand how they work in a living system. These experiments will make sure that the designed antibodies can target the amyloid protein and can effectively prevent it from forming clumps.

He hopes that these antibodies will work to stop the processes behind Alzheimer's disease before they can cause damage to brain cells. 

How will this benefit people with dementia?

This project is exploring new angles in tackling one of the major treatment targets for Alzheimer's disease - the amyloid protein. If an antibody can be developed that prevents the toxic amyloid clumps from forming, Dr Aprile hopes to work with industrial partners to turn it into a potential treatment. Therefore this work represents the first steps in an innovative approach to preventing a key process that underlies the development of Alzheimer's disease.