Immunotherapy for Alzheimer's disease: beta-amyloid plaques (shown in green) are surrounded by immune cells carrying a receptor for antibodies (red).
Image credit: Southampton University
Now, a new study suggests there may be a way to engineer antibodies so they still help clear plaques but without side effects.
The study, published in the journal Acta Neuropathologica, is the work of researchers from the University of Southampton in the UK and Lundbeck A/S, a multinational pharmaceutical company based in Copenhagen, Denmark.
Around 47.5 million people worldwide have dementia, a disease that harms memory, thinking and behavior and erodes the ability to carry on with everyday life.
The most common form of dementia is Alzheimer's disease, a feature of which is faulty protein deposits called plaques that accumulate and clog up the brain.
Immunotherapy is a promising new approach for the treatment of Alzheimer's and other diseases, but the success in the lab is proving difficult to repeat in the clinic.
The new study focuses on an immunotherapy technique that uses antibodies to stimulate the immune system to remove the brain plaques of beta-amyloid protein that are thought to be a major driver of the brain deterioration seen in Alzheimer's disease.
Clues on how to clear brain plaques without inflammation
In mice bred to develop human-like forms of Alzheimer's disease, antibodies that recognize beta-amyloid have successfully led to clearance of brain plaques and reversed declines in cognitive function.
But attempts to repeat this effect in clinical trials with human Alzheimer's patients tend to result in an inflammatory effect called amyloid-related imaging abnormalities (ARIA), which causes small bleeds and dangerous brain swelling.
To investigate this further, the team engineered three antibodies and changed some of their properties to see what effect this might have on ability to help clear beta-amyloid and induce inflammation.
After running tests in mice, the team found that the ability of an antibody to clear plaques and induce inflammation is dependent on small but precise changes to two properties: the epitope and affinity of the antibody.
The epitope is the part of the beta-amyloid molecule that the antibody is designed to recognize. Affinity is the strength of the interaction between the antibody and the epitope.
The researchers acknowledge there is still a lot of work to do to before they have antibodies that are effective at clearing amyloid plaques without causing inflammation in humans. However, their findings offer a roadmap and some clues on how to go about creating and testing them.
Senior author Dr. Jessica L. Teeling, of Southampton's Centre for Biological Sciences, says:
"New antibodies are entering the clinic for Alzheimer's disease; therefore, it is important to learn all we can from research into these novel interventions and use antibody engineering technology to optimize their effects."
Meanwhile, Medical News Today recently learned of an antibody test that may be able to detect Alzheimer's at a preventable stage. The researchers believe the test could also help detect other diseases, such as Parkinson's disease, multiple sclerosis and breast cancer.