# New BDNF Nanoparticles for Early Treatment of Alzheimer's Disease

> **NIH NIH R44** · EXQOR TECHNOLOGIES, INC. · 2024 · $995,987

## Abstract

Alzheimer's Disease (AD) represents a major chronic health problem in the US and abroad. MRI studies of AD
demonstrated a decrease in the size of the hippocampus and other brain structures associated with learning
and memory. Toxic proteins, like Aß and tau, accumulate in these brain regions, and MRS and PET imaging
studies consistently showed metabolic deficits and oxidative stress in brains of patients with AD. BDNF can
improve metabolism, promotes neuronal plasticity and restore brain functions. However, BDNF cannot easily
cross an intact blood brain barrier (BBB) and is unstable in the blood or when delivered orally. In SBIR Phase 1
& 2, ExQor developed a nanotechnology platform that provides an innovative approach for treatment of AD. It
consists of 2 components: a clathrin nanoparticle (CNP) and attached brain-derived neurotrophic factor
(BDNF). CNPs successfully bypassed the blood-brain barrier (BBB) intranasally (i.n.) and CNS concentrations
of BDNF were up to 400-fold higher than reported in previous BDNF i.n. studies. CNPs restored memory and
regenerated hippocampal regions by increasing neurogenesis, synaptogenesis, and dendritic integrity in a
mouse model of AD. CNP effects were detected in the mouse hippocampus with two different MR
neuroimaging modalities. Voxel based morphometry showed CNP-enhanced hippocampal gray matter
densities. Proton MR spectroscopy showed that CNP decreased lactate, alanine, aspartate, myoinositol and
glutathione concentrations, indicating CNP reversed anaerobic metabolism, gliosis, and oxidative stress in the
mouse hippocampus. CNP also increased choline-containing compounds associated with increased
neurogenesis and neuronal plasticity.
The goal of this effort is to scale-up production of BDNF-clathrin nanoparticles (CNPs), perform
pharmacokinetic and safety studies required for IND, and confirm efficacy in the second animal model of AD.
In Phase IIb SBIR, a series of in vivo studies will ascertain CNP distribution, safety and efficacy. TgF344-AD
rats will be treated with CNPs or placebo early in the course of the disease for 6 months, and cognitive testing
and MRI and 1H MRS will be performed after treatments. We plan to demonstrate the feasibility of this novel
nanotechnology to enhance learning and memory, increase gray matter densities, and reverse metabolic
abnormalities and oxidative stress associated with AD.
This research project will provide new, noninvasive nanotechnology tools for early treatment of AD. The new
nanotechnology will be able to enhance neuronal metabolism and plasticity, protect brain and restore brain
functions more quickly and completely than existing treatment methods, while using much lower therapeutic
drug doses and causing fewer side effects. The development of a stable, targeted molecular nanoparticle may
also provide a major new tool for research of biomarkers in AD. This novel nanotechnology may serve as the
basis for a next generation drug-delivery system that can specifi...

## Key facts

- **NIH application ID:** 10894789
- **Project number:** 5R44AG058343-06
- **Recipient organization:** EXQOR TECHNOLOGIES, INC.
- **Principal Investigator:** GORDANA D. VITALIANO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $995,987
- **Award type:** 5
- **Project period:** 2017-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894789

## Citation

> US National Institutes of Health, RePORTER application 10894789, New BDNF Nanoparticles for Early Treatment of Alzheimer's Disease (5R44AG058343-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894789. Licensed CC0.

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