Alzheimer gene therapy targeting amyloid beta oligomers

Alzheimer's is a form of dementia and affects memory, thinking, and behavior. It is a neurodegenerative disease where the aggregation of amyloid beta (Aβ) in the brain is one of the typical characteristics. In this project, we want to test immunotherapy with an antibody against aggregated Aβ oligomers.

To enable immunotherapy against Aβ oligomers, a VNAR antibody has been selected with superior binding characteristics. In a previous project, we used in vitro and in vivo assays to examine whether this antibody is expressed and whether the therapy can lead to improvements in learning and memory. Immunostaining and protein analysis showed that VNAR was present in the neurons and their medium. This indicates that the VNAR is produced by the cells and also secreted. Using an ELISA, in which the binding to Aβ oligomers was determined, the functionality of the VNAR secreted into the medium was positively tested. In short, the production and function of the VNAR were successful.

To see to what extent the brain could be transduced with our vector, in vivo experiments were conducted with an Alzheimer’s animal model. Immunostaining and protein analyses showed that 6 weeks after injection, VNAR was present. In this project, cognitive improvement was examined in an ‘Alzheimer mouse.’ At the behavioral level, a significant improvement was visible in the Morris Water Maze learning and memory test.

Although there was a slight decrease in the density of Amyloid plaques, no significant effect was observed between the group of animals treated with VNAR and the control group. To more confidently determine whether a therapeutic effect can be achieved with this new immunotherapy approach, more in vitro and in vivo tests will need to be performed.