Scientists have developed a new method for potentially treating Alzheimer’s disease and vaccinating it.
The study showed that both antibody-based treatments and protein-based vaccines developed by the team can alleviate symptoms in a mouse model of Alzheimer’s disease.
Neither product focuses on the amyloid beta protein in brain plaques commonly associated with Alzheimer’s disease, but instead targets a different form of protein that is considered highly toxic.
Amyloid beta naturally exists in the solution as highly flexible linear molecules, which can bind together to form fibers and plaques.
A large part of these molecules are shortened in Alzheimer’s disease, and some scientists now believe that these forms are the key to the development and progression of the disease.
This work is a collaboration between researchers University of Leicester The University of Göttingen Medical Center and LifeArc, a medical research charity.
Although the science is still in its early stages, if these results can be replicated in human clinical trials, it could be transformative
Professor Thomas Bayer from the University of Göttingen Medical Center said: “In clinical trials, none of the potential treatments to dissolve amyloid plaques in the brain have achieved great success in reducing the symptoms of Alzheimer’s disease.
“Some even showed negative effects. So we decided to adopt a different approach.
“We found an antibody in mice that neutralizes the truncated form of soluble amyloid beta, but does not bind to the normal form of protein or plaque.”
This antibody was adapted by Dr. Preeti Bakrania of LifeArc and his colleagues, so the human immune system will not recognize it as a foreign object, but will accept it.
Leicester When the researchers discovered how and where the humanized antibody, called TAP01_04, binds to the shortened form of amyloid β, they were surprised.
They saw that the amyloid beta protein folds toward itself in a hairpin-like structure.
If the treatment does prove to be successful, it may change the lives of many patients
Professor Mark Carr from the Leicester Institute of Structural and Chemical Biology at the University of Leicester explained: “This structure has never appeared in beta amyloid before.
“However, finding such a clear structure allowed the team to modify this region of the protein to stabilize the hairpin shape and bind to the antibody in the same way.
“Our idea is that this modified beta amyloid may be used as a vaccine to trigger someone’s immune system to make TAP01_04 antibodies.”
When testing the modified amyloid beta protein in mice, they found that the animals receiving the “vaccine” did indeed produce TAP01 type antibodies.
The antibody and the engineered beta amyloid vaccine, called TAPAS, were then tested in two different mouse models of Alzheimer’s disease.
Based on imaging techniques similar to those used to diagnose Alzheimer’s disease in humans, the researchers found that both antibodies and vaccines help restore neuronal function.
According to this study, they also help increase glucose metabolism in the brain and restore memory loss. Although they are not directly targeted, they even reduce the formation of amyloid beta plaques.
Dr. Bakrania of LifeArc said: “The TAP01_04 humanized antibody and TAPAS vaccine are very different from the Alzheimer’s disease antibodies or vaccines previously tested in clinical trials because they target different forms of protein.
“This makes them very promising as therapeutic antibodies or vaccines as a potential treatment for the disease.
“The results so far are very exciting and demonstrate the scientific expertise of the team.
“If the treatment does prove to be successful, it may change the lives of many patients.”
Professor Carr added: “Although the science is still in its early stages, if these results can be replicated in human clinical trials, then it could be transformative.
“It opens up the possibility not only to treat Alzheimer’s disease after symptoms are detected, but it is also possible to vaccinate against the disease before symptoms appear.”
Researchers are now looking for commercial partners to obtain therapeutic antibodies and vaccines through clinical trials.
The findings were published in Molecular Psychiatry.
