Gene therapy for Alzheimer’s disease

Alzheimer adenoviral gene therapy targeting amyloid beta oligomers

In this project VU University researchers in the field of Alzheimer’s joined forces with Degenrx BV to test a new therapy for Alzheimer’s disease. Alzheimer's is a form of dementia and affects memory, thinking and behaviour. It is a neurodegenerative disease in which amyloid beta (Aβ) is one of the typical hallmarks of the disease in the brain. Alzheimer’s is devastating disease and currently has no cure. People above age 80 have 20% chance of getting Alzheimer’s. This project is aimed at ultimately treating people at an early disease stage as to prevent progression.

In this project immunotherapy with an antibody against Aβ oligomers was tested. They looked at whether this antibody is expressed in the brain after viral transduction, and whether such therapy can bring about an improvement on learning and memory. This analysis showed that antibody was present in cultured neurons and in the Alzheimer's animal model. Analyses showed that the antibody was present 6 weeks after injection.  There was also glial cell activation after the injections, which may indicate that too high a dose of virus was used. Treated animals were eventually tested in a memory test, which showed that there was no memory improvement in the antibody treated animals.  

The conclusion from the experiments is that in a new study the dose should be reduced, and that the effect on memory should then be looked at again. It is also wise to look at the amount of amyloid plaques, also typical for Alzheimer’s disease. These experiments will now be carried out in a follow-up project.

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Summary
This project aimed to demonstrate that the VNAR-based AAV-mediated gene therapy is effectively working in an Alzheimer’s disease animal model as a stepping stone towards clinical evaluation in early-stage patients. This project found that VNAR antibodies are expressed in vitro and in vivo in hippocampal neurons. The high dose of virus used probably elicited unwanted glial activation as could be detected by immunostaining. Due to the high dose, memory tests with VNAR interventions were inconclusive. Next experiments will have to be performed with lower virus titer.
Technology Readiness Level (TRL)
1 - 3
Time period
21 months
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