Broad - shouldered antibodies

Developing effective approaches for the treatment of Alzheimer's disease is a difficult task, and even recently approved drugs have only a minor effect. There are several reasons for their low effectiveness, one of which is that the antibodies used do not bind to all types of toxic aggregates that cause Alzheimer's disease.

In Alzheimer's disease, the beta-amyloid protein accumulates in brain tissue and forms clots, or aggregates, that destroy nerve cells. A research team from Uppsala University led by Greta Hultqvist has previously shown that treatment with the hormone somatostatin triggers the process of destruction of the components of the unit. In a new study, an antibody has been created that can bind to toxic aggregates, preventing them from damaging nerve cells.

Antibodies that are currently being tested in clinical trials actively bind to large aggregates and ignore small ones. However, small aggregates are no less toxic than large ones, and many scientists believe that in fact they are even more dangerous, since they are more mobile. The aim of this study was to develop antibodies that can bind both large and small clots of beta-amyloid.

Antibodies use the avidity effect to bind firmly to their targets. To do this, both arms must simultaneously bind to the same molecule.

The distance between the arms of the antibodies is crucial for the size of the aggregate with which the antibody can bind firmly: if the aggregate is smaller than the distance between the shoulders, then a weak bond is formed, if larger, it binds firmly to the antibody. In the new work, the researchers obtained antibodies with shorter distances between the arms so that they bind to smaller aggregates, and also increased the size of the binding endings in order to bind aggregates more reliably.

Due to the greater avidity, the new antibody format was up to 40 times more actively bound to beta-amyloid aggregates. In addition, they picked up small aggregates, which was not previously observed in any other antibody.

The novelty was tested on cell cultures. Experiments have shown that the new antibody format can protect cells from destruction by beta-amyloid deposits. The results obtained should be confirmed in preclinical models, but it is already possible to hope that the antibodies of the new design may be more effective against Alzheimer's disease than existing ones. In addition, the new antibodies can bind other pathological protein deposits formed in various diseases, including Parkinson's disease.

Article F.Rofo et al. The novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta is published in the journal Translational Neurodegeneration.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Uppsala University: More effective treatment of Alzheimer's.