# Neuroprotective anti-inflammatory drugs as a novel combination therapy for neurological Rift Valley Fever

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $333,894

## Abstract

PROJECT SUMMARY/ABSTRACT
 Understanding the pathogenesis of neurological disorders caused by arboviruses is fundamental to the
treatment of viral encephalitis using drug or vaccine therapy. Rift Valley Fever (RVF) is a globally-important
emerging mosquito-transmitted disease that presents a significant risk to humans and livestock communities.
The potential for global spread is high due to the pervasive mosquito vectors, and emergence would cause
considerable economic damage (due to the agricultural impact) as well as fear and anxiety (due to human
illness). The most understudied clinical disease caused by RVFV is encephalitis, which causes long-term
morbidity in survivors as well as death in 50% of patients with neurological symptoms. This proposal is founded
upon 3 scientific findings from our preliminary data: 1) There are appropriate encephalitic disease animal models
after infection with a wild-type virulent strain of RVFV; 2) Overproduction of cytokines, chemokines, and matrix
metalloproteinases (MMPs) correlates with neurological disease onset; and 3) Treatment with the antiviral
therapeutic drug favipiravir is necessary but not sufficient to protect animals from lethal neurological disease.
Taken together, the objective of this proposal is to understand the role of cytokine and MMP-mediated host
inflammatory response in RVF-induced neurological disease, with the ultimate goal of designing therapeutic
interventions to prevent neuropathology. We will address this objective using three complementary specific aims:
In Aim 1, we will determine the kinetic mechanisms by which cytokines and MMPs modulate RVF CNS
inflammation. Aim 2 will develop novel in vitro modeling systems to define RVFV-CNS cell interactions and
screen therapeutic candidates. Aim 3 will test novel therapeutic regimens in a relevant animal model. This
proposal will result in an understanding of the contribution of immunopathology to RVF neurological disease.
Importantly, we will have identified a post-exposure treatment regimen to protect from neurological RVF. This
proposal represents a critical step in the event of an epidemic of this emerging pathogen.

## Key facts

- **NIH application ID:** 9915980
- **Project number:** 5R01NS101100-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Amy L Hartman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,894
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915980

## Citation

> US National Institutes of Health, RePORTER application 9915980, Neuroprotective anti-inflammatory drugs as a novel combination therapy for neurological Rift Valley Fever (5R01NS101100-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9915980. Licensed CC0.

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