Scientists target beta-amyloid molecule in search of preventative treatment strategy for Alzheimer’s disease

To combat Alzheimer’s disease, researchers at the Technical University of Munich (TUM) have developed a promising preventive therapeutic approach. They targeted in particular the biomolecule beta-amyloid, which triggers the hyperactivity of nerve cells typical of the brain disease in its early stages.

The team led by Dr. Benedikt Zott and Professor Arthur Konnerth from the TUM Faculty of Medicine and Health and Professor Arne Skerra from the TUM Faculty of Life Sciences has succeeded in developing and using a protein drug that can suppress the effects of the harmful molecule.

The study is published in Nature CommunicationsThe results obtained in laboratory mice indicate that neuronal dysfunctions could even be repaired. The researchers hope that the protein they studied, which experts call amyloid-beta-binding anticalin (H1GA), could stop the progression of this serious neurodegenerative disease at an early stage.

According to experts, 55 million people worldwide suffer from dementia, most of them Alzheimer’s disease. Every year, about 10 million new cases are diagnosed. There are currently no drugs to combat the basic mechanisms of the disease. Only symptoms such as decreased mental performance can be treated.

“We are still a long way from a therapy that can be used in humans, but the results of animal experiments are very encouraging,” says Dr. Zott. “The effect of completely suppressing neuronal hyperactivity in the early stages of the disease is particularly remarkable.”

The researchers obtained the anticalin H1GA by protein design and produced it in genetically modified bacteria of the species Escherichia coli. The active ingredient was injected directly into the hippocampal region of the brain. As far as measurable behavior was concerned, the previously hyperactive brain cells could no longer be distinguished from healthy nerve cells.

It is not yet known whether this effect can be achieved in humans outside the laboratory. In any case, a more effective form of administration of the active ingredient is currently under development.

In 2016, the active substance solanezumab, which was supposed to have a similar effect, failed in large-scale clinical trials; this was due to its different molecular structure.

Zott and colleagues also directly compared their new active ingredient with solanezumab in trials. H1GA showed more clear positive effects.