Drug Development

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Alzheimer's Disease (AD) affects 55 million globally, with current drug discovery facing high risks due to unclear mechanisms.
• The TREAT-AD Consortium aims to revitalize the AD drug development pipeline by accelerating target characterization and validation.
• The Emory-Sage-SGC-JAX TREAT-AD Center utilizes Target Enabling Packages (TEPs) to bridge the gap between target discovery and therapeutic development.

Purpose of the Study:

• To enable rapid exploration of emerging therapeutic hypotheses and novel AD targets.
• To initiate early-stage drug discovery campaigns against validated targets.
• To support NIA-funded target discovery programs in AD.

Main Methods:

• Developed an iterative target prioritization pipeline to score candidate proteins.
• Utilized a target AD risk score mapped to 19 biological domains dysregulated in AD.
• Identified and prepared experimental reagents for hypothesis testing for prioritized targets.

Main Results:

• Created TEPs for over 50 understudied AD targets.
• TEPs include bioinformatic analysis, expression constructs, purified proteins, validated cell lines, and assay development.
• Advanced targets include DHX58, SYK, DDX1, SDC4, CAPN1, ARHGEF2, and SMOC1.

Conclusions:

• All data, protocols, and reagents are publicly available on the AD Knowledge Portal without intellectual property claims.
• Target Risk Scores and biodomains are accessible via Agora.
• The TREAT-AD Center facilitates collaborative research and accelerates therapeutic development for Alzheimer's Disease.