# Targeted antibody-conjugated magnetic nanoparticles for the treatment of Alzheimer's disease

> **NIH NIH F30** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $50,520

## Abstract

ABSTRACT/PROJECT SUMMARY
Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive memory loss and
cognitive disturbances affecting over 5 million Americans. AD is hypothesized to be due to the accumulation of
two pathogenic proteins in the brain. One is the accumulation of amyloid-β (Aβ) outside of cells and the second
is the accumulation of hyperphosphorylated tau protein inside cells that eventually leads to aggregates called
neurofibrillary tangles. The aggregation of amyloid prevents normal cell signaling pathways while neurofibrillary
inhibit nutrient delivery to the neurons, both of which ultimately leads to neuronal death. Multiple AD previous
clinical trials target pathogenic Aβ species using therapeutic anti-Aβ antibodies. However, previous failures in
clinical trials demonstrate a gap in knowledge in our current understanding of the pathogenesis of AD and an
immediate need for the development of new safe therapeutic approaches, which can be applicable at the very
early stage of the disease. One major side effect in previous clinical trials is the chronic presence of high-titer
anti-Aβ antibodies in brains triggers inflammatory responses and other undesirable side effects, namely amyloid-
related imaging abnormalities including microhemorrhages (ARIA-H) and edema (ARIA-E). Since recent results
from the aducanumab clinical trial is showing immense promise, there is an urgent need for the development of
a technology to reduce these side effects. To address this challenge, which may contribute to the failures of
these previous current drug trials, we developed superparamagnetic iron oxide nanoparticles conjugated with
anti-Aβ antibodies that bind to Aβ peptides and aggregated Aβ species. These particles are paramagnetic, which
allows them to be removed by an external magnetic field in vitro. To validate the efficacy and safety of anti-Aβ
antibody conjugated SPIONs, we will use both 3D human neural cell culture models of AD, which our lab
developed previously, and transgenic AD mouse models. Combining these two technologies, we devised a
methodology to rapidly remove Aβ species using external magnetic force guided removal of anti-Aβ antibody
conjugated SPIONs in 3D cell culture of AD. The 3D cell culture model will be mostly used for testing efficacy
and the impact of the anti-Aβ antibody on Aβ-driven tau pathology while transgenic AD mice will be used to
assess the efficacy and potential toxicity in vivo. Aim 1 evaluates the use of a static magnet with SPIONs with
to reduce Aβ species in 3D culture model of AD and in an AD mouse model. The aim further investigates the
downstream tau effects of Aβ removal in the 3D culture model. Aim 2 will examine the potential of using an
alternating magnetic field to deliver therapeutic antibodies conjugated to SPIONs across the blood-brain barrier
in the AD 5XFAD mouse model. This second aim has tremendous impact on the feasibility of this technology as
a new therapeutic...

## Key facts

- **NIH application ID:** 10314932
- **Project number:** 1F30NS120499-01A1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Shen Ning
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,520
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314932

## Citation

> US National Institutes of Health, RePORTER application 10314932, Targeted antibody-conjugated magnetic nanoparticles for the treatment of Alzheimer's disease (1F30NS120499-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314932. Licensed CC0.

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