# Targeting Blood-CNS-Barrier in ALS via Apolipoprotein A1

> **NIH NIH R21** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $187,500

## Abstract

Project Summary Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal disease of widespread motor neuron degeneration in the brain and
spinal cord. Progressive impairment of the blood-CNS--barrier (B-CNS-B) represents an additional disease
mechanism. Capillary endothelial cell (EC) damage in the CNS has been shown in ALS rodent models and in
ALS patients. We demonstrated benefits of intravenously (iv) transplanted human bone marrow-derived
endothelial progenitor cells (hBM-EPCs) on functional disease outcomes and motor neurons in an SOD1 mouse
model of ALS by attenuating damage to the compromised barrier. Transplanted hBM-EPCs may also exert
positive effects by release of extracellular vesicles (EVs) and facilitate restoration of degenerated ECs through
delivery of cargo proteins. Apolipoprotein A1 (ApoA1) was determined as the most abundant high-expression
protein in EVs and may represent a therapeutically active component for EC-targeted regeneration. We showed
that ApoA1 enhanced EC survival in an ALS-like pathologic condition in vitro. The purpose of this project is to
determine whether ApoA1 facilitates endothelium homeostasis leading to B-CNS-B repair in ALS. The
significant scientific advance of this project is the demonstration that ApoA1 administration elucidates
reparative processes in B-CNS-B restoration and promotes motor neuron survival in G93A SOD1 mutant mice.
Also, the determination of reparative mechanisms underlying B-CNS-B restoration by assessing ApoA1 effects
is the novelty of this project. An important aspect of the proposed study is B-CNS-B restoration in a symptomatic
mouse model of ALS with existing barrier damage. Aim 1 will establish therapeutic efficacy of a single iv
administration of ApoA1 into symptomatic ALS mice of both genders on B-CNS-B repair by examining behavioral
disease outcomes (Aim 1A), functional (Aim 1B) barrier repair, glial cells status (Aim 1C), and motor neuron
survival (Aim 1D). Aim 2 will determine the mechanism(s) of ApoA1-mediated vascular repair in symptomatic
ALS mice by examining the pathway of this protein on endothelium integrity. This aim will address activity of the
ApoA1 protein by impeding the downstream signaling through the cytosolic PI3K/Akt pathway. The effects of
inhibiting intracellular signaling will be examined with the same outcomes as described in Aim 1 Sub-aims. Our
experimental design to determine the efficacy of ApoA1 administration is a highly translational and innovative
mechanism-based approach for repairing the damaged B-CNS-B. Positive project outcomes will evidence the
mechanistic role of ApoA1 protein in restoring EC function towards repair of the altered B-CNS-B in ALS. Even
if Aim 1 results are negative, probing ApoAI in Aim 2 via inhibitory paradigm will reveal novel ApoAI-based
approaches to optimize protein treatment. This study represents a relatively low-risk, but high-reward and
innovative protein-mediated therapy for vascular repair in ALS, thereby facilit...

## Key facts

- **NIH application ID:** 10839856
- **Project number:** 5R21NS132576-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** SVITLANA NICOLAI GARBUZOVA-DAVIS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,500
- **Award type:** 5
- **Project period:** 2023-05-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839856

## Citation

> US National Institutes of Health, RePORTER application 10839856, Targeting Blood-CNS-Barrier in ALS via Apolipoprotein A1 (5R21NS132576-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10839856. Licensed CC0.

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