A promising new approach to Alzheimer’s treatment and vaccinating against it has been developed by a team of UK and German scientists.
The research published in Molecular Psychiatry found that an antibody-based Alzheimer’s treatment and the protein-based vaccine developed by the team reduced Alzheimer’s symptoms in mouse models with the disease.
The work is a collaboration between researchers at the University of Leicester, the University Medical Center Gottingen and the medical research charity LifeArc.
New Alzheimer’s treatment shown to reduce symptoms
The amyloid beta protein in plaques in the brain is commonly associated with Alzheimer’s disease; however, the antibody and vaccine both target a different soluble – a form of a protein that is thought to be highly toxic. Amyloid beta protein exists as a highly flexible, string-like molecule in solution, which can join to form fibres and plaques. In Alzheimer’s disease, a high proportion of these string-like molecules become shortened or ‘truncated’, and scientists now believe these forms are key to the development and progression of the disease.
Professor Thomas Bayer, from the University Medical Center Göttingen, said: “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 neutralise the truncated forms of soluble amyloid beta but would not bind either to normal forms of the protein or to the plaques.”
Dr Preeti Bakrania and colleagues from LifeArc adapted this antibody so a human immune system wouldn’t recognise it as foreign and would accept it. When the Leicester research group looked at how and where this ‘humanised’ antibody, called TAP01_04, was binding to the truncated form of amyloid beta, they found the amyloid beta protein was folded back on itself, in a hairpin-shaped structure.
Professor Mark Carr, from the Leicester Institute of Structural and Chemical Biology at the University of Leicester, explained: “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 stabilise 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.”
Testing the new treatment
The team tested the engineered amyloid beta protein in mice and found that those mice who received this ‘vaccine’ did produce TAP01 type antibodies.
Following this, the Gottingen Group tested both the ‘humanised’ antibody and the engineered amyloid beta vaccine, called TAPAS, in two different mouse models of Alzheimer’s disease. Using similar imaging techniques used on Alzheimer patients, they discovered that both the antibody and vaccine helped restore neuron function, increase glucose metabolism in the brain, restore memory loss, and reduce amyloid beta plaque formation.
LifeArc’s Dr Bakrania said: ‘’The TAP01_04 humanised 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.”
Professor Mark Carr added: “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.”
The researchers are looking to find a commercial partner to take the antibody and vaccine through clinical trials.
