# A Dominantly Inherited AD network In Vitro Trial with a Gamma-Secretase Modulator

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

Alzheimer’s disease (AD) is defined neuropathologically by extracellular plaques composed of
β-amyloid (Aβ42) and intracellular tangles consisting of hyperphosphorylated forms of the
microtubule-associated protein tau. Aβ accumulation and hyperphosphorylation of tau are
recognized as key events leading to full blown AD neuropathology. Here we propose
comprehensive in vitro analysis of a unique set of novel small molecule drugs known gamma-
secretase modulators (GSMs) to further explore AD therapeutics. This proposal will focus on
testing an optimal lead clinical candidate for efficacy in human neurons aimed at halting Aβ42-
related pathologies AD. Our overarching hypothesis is GSM therapy aimed to disrupt production
of Aβ42 will be an efficacious treatment approach for prodromal or early AD, as well as sporadic
late-onset AD. The goal of this project is to validate target engagement in human neurons from
selected patients.

## Key facts

- **NIH application ID:** 9962891
- **Project number:** 5I01RX002259-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Steven Lee Wagner
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962891

## Citation

> US National Institutes of Health, RePORTER application 9962891, A Dominantly Inherited AD network In Vitro Trial with a Gamma-Secretase Modulator (5I01RX002259-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962891. Licensed CC0.

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