Investigating a rheumatoid arthritis drug as a potential treatment for Alzheimer's disease

Read about a research project we funded into a double-blind, placebo-controlled study of the affect of a TNFα antibody, Etanercept, on microglial activation in amyloid PET positive patients with mild cognitive impairment due to AD-intermediate likelihood.

Lead Investigator: Professor Clive Holmes

Institution: University of Southampton

Grant type: Project grant 

Duration: 3 years

Amount: £362,000 (Split 50:50 with the Alzheimer's Drug Discovery foundation. This project is part of a larger EU funded collaborative project called INMiND, project grant agreement number: HEALTH-F2-2011-278850)

What do we already know?

There is growing evidence that the immune system plays a role in the development of Alzheimer's disease. Research in this area has focused on specialised immune cells in the brain called microglia.  

Usually, when the brain is affected by an infection, microglia become 'activated' and begin releasing chemicals to help fight the infection. One of the hallmarks of Alzheimer's disease is the presence of sticky clumps of a protein called amyloid around the brain cells. Evidence from using animals that show symptoms of Alzheimer's disease indicates that the amyloid clumps may be responsible for activating the microglia. If the brain is then subjected to an infection, the microglia become overactive and release chemicals at levels that cause damage to the cells. This causes accelerated Alzheimer's disease progression in the animals.  

What does the project involve?

An Alzheimer's Society project given to Professor Holmes previously found that infections can speed up memory decline in people with Alzheimer's disease. One of the chemicals that are released by microglia in response to an infection is called TNFα. Drugs that lower the levels of TNFα are already approved for use in the treatment of rheumatoid arthritis, which is caused by a faulty immune system. This project builds on a small clinical trial to determine whether one of these drugs, Etanercept, was safe to use in people with Alzheimer's disease.  

Professor Holmes and his collaborators are now planning on conducting another small trial to determine whether Etanercept can confer any benefit to people affected by mild cognitive impairment. This trial will give 46 volunteers either Etanercept or a placebo drug every week for a year. The researchers will use the results to determine whether Etanercept can reduce the activation of microglia in people with mild cognitive impairment. It also aims to see whether treatment with Etanercept can help to improve cognitive ability in the volunteers.   

How will this benefit people with dementia?

Treatments available to people with Alzheimer's disease are currently limited. However, it can take up to 20 years to develop a drug from scratch.

This trial is an example of drug repurposing, which involves taking pre-existing drugs for other conditions and determining whether they can benefit people with dementia. This is one of the key purposes of our Drug Discovery programme. This method can help to speed up the process of drug development as the existing drugs have already passed several checkpoints. 

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