# Targeted Immunotherapy in a Nonhuman Primate Model of Alzheimers Disease

> **NIH NIH R24** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $267,811

## Abstract

PROJECT SUMMARY
For 22 years, the Nonhuman Reagent Resource (NHPRR) has produced and distributed high
quality NHP antibodies to NIH investigators where there are no commercial alternatives.
Although most program reagents were validated and engineered for use in Old World species
that are commonly used in preclinical biomedical research, a new targeted effort, funded through
the R24 mechanism, was launched in 2020 to create and characterize antibodies for New World
primate studies. This grant covers the development and production of squirrel monkey and
marmoset monospecific immunoglobulins that are suitable for in vivo administration and
carefully monitored for contaminants that can compromise animal safety and experimental
integrity.
Squirrel monkeys are natural NHP models for Alzheimer’s disease (AD) due to an age-associated
neurodegenerative decline that pathologically resembles AD with cerebral amyloid angiopathy
(CAA). One formidable barrier to applying immunotherapeutics, other macromolecular drugs, or
even some small molecule inhibitors to treat AD is the impenetrable nature of the blood-brain
barrier (BBB) that excludes most drugs from the brain parenchyma. In this supplement
application, we propose to develop a bispecific antibody capable of transversing the BBB through
receptor-mediated transport (RMT) and targeting AD-relevant protein beta-secretase (BACE1).
This reagent will be rigorously tested in vitro and in vivo to measure any therapeutic gains
through RMT and validate the technology in squirrel monkeys. The final RMT-BACE1 squirrel
monkey IgG will be offered and distributed to AD investigators through the program website.
Furthermore, this effort will establish methods to generate RMT bispecific antibodies for
neotropical primate immunoglobulins that can be broadly applied to other AD immunotherapy
candidates or imaging studies.

## Key facts

- **NIH application ID:** 10497425
- **Project number:** 3R24OD028257-03S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Kathleen Engelman
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $267,811
- **Award type:** 3
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497425

## Citation

> US National Institutes of Health, RePORTER application 10497425, Targeted Immunotherapy in a Nonhuman Primate Model of Alzheimers Disease (3R24OD028257-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10497425. Licensed CC0.

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