LEICESTER, United Kingdom — A vaccine for Alzheimer’s disease may sound farfetched at first, but British and German scientists suggest a vaccine for the most common form of dementia may one day be a reality. Researchers from Leicester University, the University Medical Center Göttingen, and the medical research charity LifeArc report a newly developed Alzheimer’s approach is showing serious promise – both as a concrete treatment for the disorder and as a means of producing an effective vaccine.
Both the antibody-based treatment and the protein-based vaccine created by the study’s authors successfully mitigated Alzheimer’s symptoms in a series of dementia mouse models.
The development and onset of Alzheimer’s has a strong connection to the buildup of amyloid beta protein plaques in the brain. However, scientists in this study chose to focus on a different soluble form of the protein they consider highly toxic.
“In clinical trials, none of the potential treatments which dissolve amyloid plaques in the brain have shown much success in terms of 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 the truncated forms of soluble amyloid beta, but would not bind either to normal forms of the protein or to the plaques,” says Thomas Bayer from the University Medical Center Göttingen in a media release.
‘Humanized’ antibody provides big surprises
The research team then took special care to change this antibody so that the human immune system wouldn’t react to it as a foreign threat. After observing how and where this “humanized” antibody (TAP01_04) attached itself to the shortened form of amyloid beta, it became clear the amyloid beta protein folded back on itself — similar to a hairpin-shaped structure. This came as a big surprise to the scientists.
“This structure had never been seen before in amyloid beta. However, discovering such a definite structure allowed the team to engineer this region of the protein to stabilize the hairpin shape and bind to the antibody in the same way. Our idea was that this engineered form of amyloid beta could potentially be used as a vaccine, to trigger someone’s immune system to make TAP01_04 type antibodies,” explains Professor Mark Carr, from the Leicester Institute of Structural and Chemical Biology.
Next, researchers tested the specially developed amyloid beta protein on mice. Sure enough, rodents given this “vaccine” indeed began developing TAP01 type antibodies.
Vaccine reverses several Alzheimer’s symptoms
Study authors used both the “humanized” antibody and the developed amyloid beta vaccine (called TAPAS) on two different mouse models of Alzheimer’s disease. Similar imaging techniques to those used to diagnose dementia in humans revealed both the antibody and the vaccine helped to restore neuron function, increase glucose metabolism in the brain, and restore memory loss. Importantly, amyloid beta plaque formation declined as well, even though the vaccine didn’t actually target those proteins.
“The TAP01_04 humanized antibody and the TAPAS vaccine are very different to previous antibodies or vaccines for Alzheimer’s disease 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 the disease either as a therapeutic antibody or a vaccine. The results so far are very exciting and testament to the scientific expertise of the team. If the treatment does prove successful, it could transform the lives of many patients,” adds Dr. Preeti Bakrania from LifeArc.
“While the science is currently still at an early stage, if these results were to be replicated in human clinical trials, then it could be transformative. It opens up the possibility to not only treat Alzheimer’s once symptoms are detected, but also to potentially vaccinate against the disease before symptoms appear,” Prof. Carr concludes.
Moving forward, study author are looking for a commercial partner to help initiate clinical trails for the therapeutic antibody and the vaccine.
The findings appear in the journal Molecular Psychiatry.