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Drug Development.

Karina Leal1, Elizabeth L Zoeller2, Gregory A Cary3

  • 1Sage Bionetworks, Seattle, WA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

The TREAT-AD Center accelerates Alzheimer's disease (AD) drug discovery by creating Target Enabling Packages (TEPs) for novel therapeutic targets. These packages provide essential reagents and data to validate new drug hypotheses and advance treatments for AD.

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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.