Research has found a new approach to address the prevention and treatment of Alzheimer’s disease; Specifically, they have developed a protein-based vaccine and a therapy based on antibodies, which have managed to reduce Alzheimer’s symptoms in animal models (mice) of this type of dementia, according to the results published in Molecular Psychiatry.
The study was carried out by scientists from the University of Göttingen in Germany and the University of Leicester in the UK, in collaboration with the medical research charity LifeArc. In this case, the researchers did not focus on the amyloid beta protein that accumulates in plaques in the brain and is associated with the onset of the disease, but rather the antibody and the vaccine target a different soluble form of this protein that It is considered very toxic.
New therapeutic approach to neutralize amyloid beta protein
One of the main characteristics of Alzheimer’s disease is the accumulation of amyloid plaques in the brain. Amyloid beta protein occurs naturally in different forms in the brain, and one of these can bind together into plaques that accumulate between nerve cells, but it can also occur in shorter or “truncated” soluble forms that some scientists believe to be are key to the development and progression of this dementia.
If these results are reproduced in human clinical trials, it opens the possibility not only of treating Alzheimer’s, but also of potentially vaccinating against the disease.
As Professor Thomas Bayer of Göttingen University Medical Center explained, “In clinical trials, none of the potential treatments that dissolve amyloid plaques in the brain have been shown to be very successful in reducing Alzheimer’s symptoms. Some have even shown negative side effects. So we decided on a different approach. We identified an antibody in mice that would neutralize truncated forms of soluble amyloid beta, but would bind neither to normal forms of the protein nor to plaques.”
Dr. Preeti Bakrania and colleagues at LifeArc tailored this antibody to prevent it from being identified as foreign by the human immune system, and when the Leicester team looked at how and where this ‘humanised’ antibody – dubbed TAP01_04 – bound to the truncated form of amyloid beta, they found to their surprise that the amyloid beta protein was folded back on itself in a hairpin-shaped structure.
A structure that, according to Professor Mark Carr, from the Institute of Structural Biology and Chemistry at the University of Leicester, “has never been seen before in amyloid beta. And he adds that “the discovery of such a defined structure allowed the team to design this region of the protein to stabilize the hairpin shape and bind the antibody in the same way. Our idea was that this engineered form of beta amyloid could be used as a vaccine, to cause someone’s immune system to produce TAP01_04-type antibodies.”
When they tested modified amyloid beta protein in mice, they found that animals given this “vaccine” produced TAP01-type antibodies. The Göttingen team then tested both the “humanised” antibody and the modified amyloid beta vaccine – called TAPAS – in two different mouse models of Alzheimer’s disease. And using imaging techniques similar to those used to diagnose Alzheimer’s in people, they discovered that both the antibody and the vaccine helped restore neuronal function, increase glucose metabolism in the brain, restore memory loss and decrease the formation of amyloid beta plaques.
“The humanized TAP01_04 antibody and the TAPAS vaccine target a different form of the protein. This makes them really promising as a potential treatment for Alzheimer’s.”
Dr. Bakrania stated that “the TAP01_04 humanized antibody and TAPAS vaccine are very different from previous Alzheimer’s disease antibodies or vaccines that have been tested in clinical trials, because they target a different form of the protein. This makes them really promising as a potential treatment for disease, either as a therapeutic antibody or as a vaccine. The results obtained so far are very interesting and demonstrate the team’s scientific expertise. If the treatment is successful, it could transform the lives of many patients”, she highlights.
Professor Carr concludes that “although the science is still at an early stage, if these results were replicated in human clinical trials, they could be transformative. He opens up the possibility of not only treating Alzheimer’s once symptoms are detected, but also potentially vaccinating against the disease before symptoms appear,” he says.
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