# Squirrel Monkey Breeding and Research Resource - Administrative Supplement (Nehete NKT Cell Activation)

> **NIH NIH P40** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $404,346

## Abstract

Project Summary
Extensive evidence suggests that dysregulation of innate immunity plays a key role in AD pathogenesis. It has
been increasingly acknowledged that tightly regulated stimulation of innate immunity processes and specific
microglia/macrophage activation can be neuroprotective depending on the stimulus and the environment. Toll-
like receptors (TLRs) are a family of innate immune regulators known to play an important role in governing the
phenotypic status of microglia. Major drawbacks of current immunotherapeutic approaches, including the
recently FDA-approved aducanumab, are limited effectiveness against CAA and increased incidence of CAA-
linked complications, such as amyloid-related imaging abnormalities (ARIA). CAA, for which there is no
treatment, is present in nearly all AD cases and promotes rapid cognitive decline. Our initial data using a more
proximate non-human primate (NHP) model of sporadic AD amyloid pathology, squirrel monkey (SQM), which
develops abundant CAA in all aged animals (unlike other primates), indicates that treatment with CpG ODN
Class C safely ameliorates CAA while promoting cognitive benefits. This proposal tackles a new perspective of
innate immunity of Natural Killer T (NKT) cells in squirrel monkey. This project is significant because it is the
first in the field to study the mechanism of NKT cell mediated activation of innate immune cells in squirrel
monkey. Proposed studies will investigate the molecular mechanisms of delivery the synthetic lipid α-GalCer to
activation of NKT leading progressively enhancing innate/adaptive immune responses in cytokines production
and DC activation. Data generated from the proposed studies in squirrel monkey model will form the basis for
designing molecular mechanism-driven innovative strategies to garner the adjuvant potential of NKT cells
approaches with clinical utility to Alzheimer’s disease (AD). The successful completion of this project will
enable us to test the novel concept of immunomodulation in primate models, a critical step before studies in
human clinical trials.

## Key facts

- **NIH application ID:** 10496685
- **Project number:** 3P40OD010938-42S1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** WILLIAM D HOPKINS
- **Activity code:** P40 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $404,346
- **Award type:** 3
- **Project period:** 1997-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496685

## Citation

> US National Institutes of Health, RePORTER application 10496685, Squirrel Monkey Breeding and Research Resource - Administrative Supplement (Nehete NKT Cell Activation) (3P40OD010938-42S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10496685. Licensed CC0.

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