In the battle against Alzheimer’s, researchers may have found a new focus. A study published in Molecular Psychiatry reports promising results for two new treatments that reduced symptoms of the disease in mice—not by attacking the amyloid beta protein in plaques (commonly associated with Alzheimer’s) but by targeting a different soluble form of the protein.
While amyloid beta protein exists in the brain naturally – usually as flexible molecules in a string-like shape – the same protein can also be found in a different forms: shortened or “truncated” soluble versions, which could unlock some of the mysteries about the development of the disease.
“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,” said Thomas Bayer, MD, professor at Germany’s University Medical Center Göttingen, in a press release. “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.”
The university researchers worked with collaborators from medical research charity LifeArc to create an adapted version of the antibody the human body would accept. The team saw that the new antibody – called TAP01_04 – was binding to these shortened forms of the proteins, causing them to fold back on themselves, creating a structure resembling a hairpin.
“This structure had never been seen before in amyloid beta,” said Professor Mark Carr, with the University of Leicester, another study partner. “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.”
This potential treatment led the team to test its effectiveness as a “vaccine” of sorts in mice and found that the mice that were administered the engineered protein produced antibodies. Science Daily writes they then found that both the antibody treatment and the vaccine helped to “restore neuron function, increase glucose metabolism in the brain, restore memory loss and – even though they weren’t directly targeted – reduce amyloid beta plaque formation.”
The research is revealing the differences between these two new treatments and previous antibodies and Alzheimer’s vaccines previously tested in trials.
“They target a different form of the protein,” said LifeArc’s Preeti Bakrania, PhD. “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.”
The next steps include finding a commercial partner to allow the team to evaluate both the antibody and the vaccine in human clinical trials.
