# Modeling host susceptibility factors in Acute Flaccid Myelitis

> **NIH NIH R03** · HUGO W. MOSER RES INST KENNEDY KRIEGER · 2021 · $82,264

## Abstract

Project Summary/Abstract
Modeling host susceptibility factors in Acute Flaccid Myelitis
Acute flaccid myelitis (AFM) is a poliomyelitis-like neuroinfectious illness of children whose prevalence has
increased dramatically in recent years, occurring in biennial outbreaks in the Unites States since at least 2014.
The consequences of AFM are often severe and debilitating lifelong paralysis that may also include respiratory
failure. Despite its striking similarity to polio, little is known about disease pathogenesis and few effective
treatment options exist. AFM has been connected to neurotropic non-polio enteroviruses, especially
Enterovirus D68 (EV68). However, the vast majority of cases of EV68 infections cause mild non-specific viral
symptoms or a respiratory syndrome, while only a small minority of patients become paralyzed as a result of
spinal motor neuron infection. This observation suggests that the development of AFM requires the
intersection of viral infection and host factors that are permissive to neuropathogenesis. We will therefore
generate induced pluripotent stem cell (iPS) lines from tissues previously donated by AFM patients, and use
these to model AFM resulting from EV68 infection in vitro. The initial experiments within the scope of this
application will focus on spinal motor neurons, due to the fact that motor neuron death is the proximate cause
of paralysis in AFM patients, and evidence for direct motor neuron infection by EV68. We will characterize the
composition and reproducibility of AFM patient derived and control iPS lines differentiated into spinal motor
neurons, and determine the baseline susceptibility of the neurons to a variety of cellular stressors. These
studies will set the stage for future experiments of EV68 infection of patient-derived iPS motor neurons to
better understand host factors that are permissive of viral infection and motor neuron death and dysfunction.
The result of this work will be a model system for AFM that faithfully reproduces the affected cell type, in
human cells, and on a genetic background with proven susceptibility to disease. The iPS lines will also be
capable of modeling other disease-relevant cell types in the future. These cell lines will represent a unique and
valuable resource to the AFM research community.

## Key facts

- **NIH application ID:** 10569834
- **Project number:** 7R03NS118061-02
- **Recipient organization:** HUGO W. MOSER RES INST KENNEDY KRIEGER
- **Principal Investigator:** Matthew J Elrick
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $82,264
- **Award type:** 7
- **Project period:** 2021-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569834

## Citation

> US National Institutes of Health, RePORTER application 10569834, Modeling host susceptibility factors in Acute Flaccid Myelitis (7R03NS118061-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10569834. Licensed CC0.

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