Antibodies designed by computers target Alzheimer’s protein

21 June 2017

Science Advances: Selective targeting of primary and secondary nucleation pathways in Aβ42 aggregation using a rational antibody scanning method

Researchers from the University of Cambridge have employed a new strategy for the design and creation of antibodies against the hallmark Alzheimer’s protein, amyloid. Their early findings in worms called nematodes, show that the antibodies could stop the clumping together of amyloid. Their findings are published in Science Advances today (21 June 2017).

Antibodies are the body’s natural defence against threats, such as infections. The body generates antibodies in huge quantities and variety, in the hope that one type will recognise the invader and signal to the immune system to destroy it. In recent years, researchers have turned to antibodies as potential treatments for disease, creating antibodies to treat diseases like multiple sclerosis and some forms of cancer. Scientists are also exploring antibodies as potential treatments for Alzheimer’s disease, however these trials have run into issues, which are thought, in part, to be due to detrimental inflammatory reactions triggered by the antibodies.

In this study, a team of researchers from the University of Cambridge have used computer design methods to create smaller versions of antibodies, which only contain the portion that binds to the target of choice, and lacks the part of the antibody that triggers immune responses. The researchers then tested these small antibodies to see if they could interfere with the way that amyloid proteins begin to clump together. By studying amyloid in a dish in the laboratory, they revealed that some versions of the antibodies were able to block the formation of small seeds of amyloid, which are thought to be an early stage in the process.

The team then tested these antibodies in a small nematode worm called C.elegans that has been bred to have the human form of the amyloid protein in their muscle cells. These worms normally show problems with their movement due to the amyloid. When the worms were given the antibodies, these movement problems were reversed, suggesting that the antibodies had a beneficial effect on amyloid.

Dr David Reynolds, Chief Scientific Officer at Alzheimer’s Research UK, said:

“Antibodies that target amyloid in the brain are a promising approach for tackling Alzheimer’s disease. Using innovative computer design methods, the Cambridge team has shown that they are able to generate small antibodies to block key stages of amyloid build-up but these findings are at a very early stage. While this is an important first step, there is a long road between studies involving worms and cells and knowing if an experimental approach can provide benefit to people with dementia. Only more research will tell whether this type of antibody represents a new advance that could bring welcome advantages over what has already been tried.

“There are currently no treatments that are able to stop or slow the progression of Alzheimer’s or protect the brain from the damage of the disease. With over 500,000 people in the UK living with Alzheimer’s, and that number set to rise, it is vital that we continue to invest in research so that promising new findings like these can be translated towards medications that will change lives.”