Bill Lu with the Bioengineering Department has received a $513,740 award from NIH
Alzheimer's disease (AD) is the most common cause of dementia, contributing to 60-80% of cases. This progressive and debilitating disorder places a considerable burden on individuals and strains healthcare systems. Currently, more than 6 million Americans are living with Alzheimer's, incurring an annual cost exceeding $300 billion for AD and related dementias. The condition is attributed to the abnormal accumulation of amyloid-beta (Aß) plaques in the brain, and existing therapeutic approaches have demonstrated limited success in halting or reversing AD progression.
This proposal aims to address this challenge by developing an Exosome-Based Nano-Scavenger (EBNS) with surface-modified characteristics for the targeted removal of Aß. Through a comprehensive approach, we will genetically engineer exosomes to exhibit both Aß-targeting and Aß-digesting enzymes on their outer surface, leveraging endogenous biogenic pathways. The research project comprises three specific aims to develop and validate EBNS for precise Aß removal in AD. Specific Aim 1 involves crafting a genetic strategy to present both Aß-targeting and Aßdigesting enzymes on exosome surfaces, validated through cultured human cells using real-time monitoring and co-localization analysis. Specific Aim 2 seeks to establish efficient production and isolation protocols for surface-modified scavenger exosomes, through molecular trafficking, enzyme quantification, and advanced transcriptomic and proteomic analyses.
Finally, Specific Aim 3 involves the production of therapeutic exosomes from distinct cell sources, evaluating safety and effectiveness through molecular and cellular models, and creating assays to assess the targeting and digesting abilities of scavenger exosomes. The successful completion of this project is expected to yield an innovative therapeutic approach for AD, providing a targeted and efficient method for Aß plaque removal. The development of EBNS has the potential to significantly impact the field of neurodegenerative diseases, potentially paving the way for future clinical trials and therapeutic interventions.