Increase of ADAM10 Protein Expression in the Brain as an Alzheimer’s Disease Therapeutic

Principal Investigator

Project Goals

The research team aims to determine if adeno-associated virus (AAV)- or antisense oligonucleotide (ASO)-mediated increase of ADAM10 expression attenuates Alzheimer's disease-related pathogenesis in mouse models.

Project Summary

ADAM10 is an enzyme that prevents the generation of amyloid-beta, the main component of senile plaques in Alzheimer’s disease brains. Previous studies consistently showed that loss of ADAM10 function increases Alzheimer’s risk, suggesting that increasing ADAM10 expression can be a promising therapeutic target. This study will test if brain-selective modulation of ADAM10 expression affects Alzheimer’s pathogenesis and develop an experimental antisense oligonucleotide drug that increases ADAM10 expression for Alzheimer’s treatment. 

If successful, Dr. Suh and others could screen FDA-approved drugs or other medicinal libraries to identify small molecule compounds that increase ADAM10 expression and develop them as Alzheimer’s drugs. In addition, ADAM10 antisense oligonucleotides identified from the proposed study can be optimized for human sequences and further tested and developed for Alzheimer’s treatment. 

Publications

First published on: July 31, 2024

Last modified on: September 11, 2024