# FGF-2 mimetic peptides as pleuripotent mitigators of ARS and DEARE

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $296,078

## Abstract

A nuclear blast or other mass casualty radiation event will necessarily cause multiorgan radiation
toxicities compounded by physical trauma and thermal burns. Deaths will result from complex and combined
organ injuries that occur in a time- and dose-dependent manner. While the strategic national stockpile includes
agents for hematological acute radiation syndrome (H-ARS), no candidates are approved for gastrointestinal
ARS (GI-ARS) and few if any candidates are approved for other organs. As cutaneous radiation injury [CRI
(blistering, bleeding)] when combined with H/GI-ARS can lead to death, an agent that aids multiple epithelial
tissues for combined injuries would be an ideal medical countermeasure. In light of the far-reaching potential of
FGFs, we developed an FGF-2 peptide mimetic, FGF-PT; this alternative to the full-length protein is
economical, easily scaled and synthesized, and has a long storage life. We hypothesize that the pluripotent
effects of FGF-PT on epithelial, mesenchymal, and endothelial cells, which include preservation and
proliferation of progenitor cells, maintenance of normal cellular maturation and function, and improved
tissue perfusion, will mitigate combined radiation injury syndromes. We propose to test this hypothesis
through the following Specific Aims:
 Aim 1: We will move FGF-PT toward an investigational new drug (IND) application for GI-ARS. We
have already discussed the pre-IND process with representatives of NIAID, FDA, and BARDA. Based on this
meeting, we propose a 6-step process to confirm mitigation benefit and mechanism of action in a GI-ARS/H-
ARS model in Wistar Rats. Studies will include pharmacokinetics (PK), pharmacodynamics (PD), and toxicity
testing in rats followed by PK and PD in Rhesus macaques to determine the drug dose and schedule for full
good laboratory practice (GLP) testing in rats and macaques in separate follow-up studies.
 Aim 2: We have shown that FGFs can mitigate radiation dermatitis and improve platelet function
following irradiation. In this aim, we will elucidate the role of both systemic and topical FGF-PT for CRI using an
NIH Swiss model (strontium-90 beta burn) and Göttingen minipig model. In the minipig, we will test our models
for allometric scaling between mouse, rat, monkey, and pig, and employ a radiation burn healing model (16
sites of 4x4 cm /minipig) developed by Core B.
 At the completion of Year 3, we expect to have sufficient knowledge of dose, schedule, mechanism of
action, human relevance, and safety to design a “pivotal” study for both the rat and monkey, according to the
Animal Rule, for GI-ARS under GLP conditions. Funding for that study will be sought in Year 4. Near the
completion of Year 4, we expect to have similar evidence for CRI. While minipigs are expected to play a key
role, the CRI NIAID meeting this month (May 2019) has not yet recommended a model design. In Year 5, we
will refine our approach to meet criteria more clearly defined at that time for FDA ...

## Key facts

- **NIH application ID:** 10401462
- **Project number:** 5U19AI150574-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** PAUL OKUNIEFF
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $296,078
- **Award type:** 5
- **Project period:** 2020-06-16 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401462

## Citation

> US National Institutes of Health, RePORTER application 10401462, FGF-2 mimetic peptides as pleuripotent mitigators of ARS and DEARE (5U19AI150574-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401462. Licensed CC0.

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