Potential vaccine for Alzheimer’s disease shows promise in clinical trial on mice

Scientists have reported a newly-developed vaccine for Alzheimer’s disease, suggesting that it has shown some serious promise as both a treatment and a vaccine.

The protein-based vaccine and antibody-based treatment were involved in the study by researchers from the United Kingdom’s Leicester University, Germany’s University Medical Center Göttingen, and the medical research charity LifeArc.

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The study saw the successful mitigation of Alzheimer’s symptoms in a series of experiments on dementia mouse models.

Rather than focus on the amyloid beta protein in plaques in the brain, which are commonly associated with Alzheimer’s disease, the antibody treatment and vaccine both target a different soluble – form of the protein, that is thought to be highly toxic, according to a statement released by researchers.

Amyloid beta protein naturally exists as highly flexible, string-like molecules in solution, which can join together to form fibers and plaques. In Alzheimer’s disease, a high proportion of these molecules become shortened or “truncated,” and some scientists now think that these forms are key to the development and progression of the disease.

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“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,” said Professor Thomas Bayer from the University Medical Center Göttingen.

“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,” he added.

The team of scientists then decided to adapt this antibody so that the human immune system would not react to it as a foreign threat. When the Leicester research group looked at how and where this “humanized” antibody (TAP01_04) was binding to the amyloid beta, they saw that the amyloid beta protein was folded back on itself, in a hairpin-shaped structure.

“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,” said Professor Mark Carr, from the Leicester Institute of Structural and Chemical Biology.

When the research team tested the engineered amyloid beta protein in mice, they found that the mice who received the potential ‘vaccine’ produced TAP01 type antibodies.

“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,” said LifeArc’s Dr. Preet Bakrania.

“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.”

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