# Multi-pronged therapy for immune system regeneration and recovery in a FIP model of MIS-C

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $196,510

## Abstract

This R21 proposes to fill a major scientific gap by investigating a new therapeutic approach for multisystem
inflammatory syndrome in children (MIS-C) using an innovative and clinically relevant feline model. We
propose to test a novel multi-pronged therapeutic paradigm targeting viral replication, lymphoid tissue injury
and hyper-inflammatory host response in cats with naturally occurring feline infectious peritonitis (FIP) to
accelerate viral clearance and immune restoration. Our long-term objective is to develop new therapeutic
approaches for the treatment of MIS-C. The overall objectives of this proposal are to test a novel multi-pronged
chemo-biologic therapeutic strategy and determine its underlying mechanism of action in a clinically relevant
animal model. The central hypothesis is that a combined GS-441524-multipotent stem/stromal cells (MSC)
therapy synergistically restores injured lymphoid tissues, decreases systemic inflammation and enhances
specific anti-coronavirus (CoV) immunity in cats with FIP. The rationale for this project is supported by our
preliminary data indicating that GS-441524 is a potent anti-CoV agent, and that MSC have a novel role in viral
infections by enhancing anti-viral immunity, dampening systemic inflammation and regenerating lymphoid
tissue structure and function. The central hypothesis will be tested by pursuing two specific aims: 1) Determine
the effect of GS-441524-MSC combination treatment on viral loads, lymphoid tissue injury and repair, and
elucidate the molecular networks that govern its mechanism of action; and 2) Determine the effect of GS-
441524-MSC combination treatment on T cell activation/exhaustion, inflammation and lymphocyte depletion in
peripheral blood compartment of cats with FIP. To test our hypothesis we will enroll client owned cats with FIP
into a double blinded trial with two experimental groups: GS-441524 only, or a combined GS-441524 -MSC
treatment. Blood, effusion and lymph node tissue samples will be serially collected throughout the study
timeline. Parallel samples will be collected from healthy controls. We will further leverage our bio-banked
tissues from cats with FIP that succumbed to the disease. Under the first aim we will determine the role of the
combined treatment approach in inducing IL-7, IFN type-1 and antigen presentation pathways within lymphoid
tissues to mitigate lymphoid depletion and mount an effective and balanced immune response to CoV
infection. For the second aim, we will determine the role of the combined treatment approach in inhibiting
lymphocyte apoptosis and T cell exhaustion in peripheral blood, and reducing systemic inflammation. The
proposed research is innovative because it will determine how monotherapy is affecting immune recovery, and
if MSC can enhance and accelerate viral clearance and lymphoid tissue regeneration in a clinically relevant
animal model of MIS-C. The proposed research is significant because it is expected to provide a strong
scie...

## Key facts

- **NIH application ID:** 10706865
- **Project number:** 5R21HD106027-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Amir Kol
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,510
- **Award type:** 5
- **Project period:** 2021-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10706865

## Citation

> US National Institutes of Health, RePORTER application 10706865, Multi-pronged therapy for immune system regeneration and recovery in a FIP model of MIS-C (5R21HD106027-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10706865. Licensed CC0.

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