# Therapeutic targeting of growth factor receptors to treat Mucormycosis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $514,361

## Abstract

PROJECT SUMMARY/ABSTRACT
Mucormycosis is a deadly invasive infection caused by several fungal organisms belonging to the subphylum
Mucormycotina, order Mucorales. The major risk factors include uncontrolled diabetes mellitus that results in
hyperglycemia and ketoacidosis (DKA), other forms of acidosis, treatment with corticosteroids, solid organ or
bone marrow transplantation, neutropenia, trauma and burns (e.g., wounded soldiers in Iraq and Afghanistan),
malignant haematological disorders and deferoxamine therapy in patients receiving haemodialysis. The
infection is generally acquired by inhalation of spores that are ubiquitous in nature and cause either rhino-
orbital (almost exclusively in DKA patients) or pulmonary (mainly in neutropenic leukemic patients) disease.
The treatment options for Mucormycosis are limited. There are currently no vaccines and only two antifungal
agents approved by the USA FDA to treat this disease. The first is Amphotericin B (AmB) which has serious
adverse effects, including nephrotoxicity, and very limited clinical success. Isavuconazole was recently
approved to treat mucormycosis but it is not superior to AmB treatment. In the absence of surgical removal of
the infected focus (such as excision of the eye in patients with rhinocerebral mucormycosis), antifungal therapy
alone is rarely curative. Even when surgical debridement is combined with high-dose antifungal therapy, the
mortality associated with mucormycosis is >50%. In patients with prolonged neutropenia or disseminated
disease, mortality is 90-100%. Furthermore, since there are no federal requirements to report fungal infections,
the true prevalence of mucormycosis is likely to be much higher than currently reported. The unacceptably high
mortality rate, limited options for therapy and the extreme morbidity of highly disfiguring surgical therapy make
it imperative to look for alternative strategies to treat and prevent mucormycosis. Our recently published work
suggests that Mucorales species engage host cell receptors in order to invade host tissue through the vascular
endothelium and the pulmonary epithelium. In Aim 1, we will explore the therapeutic potential of blocking the
interaction between Mucorales fungi and host cell receptors. Aim 2 will focus on identifying and characterizing
fungal-encoded drug targets with the goal of validating additional targets for novel, desperately needed anti-
fungal therapies. The ultimate goal of the work proposed here is to develop novel antifungal strategies to either
kill the fungus or disrupt molecular interactions that are important for disease progression of pulmonary
mucormycosis.

## Key facts

- **NIH application ID:** 9932341
- **Project number:** 5R01AI141360-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Vincent Michael Bruno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $514,361
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932341

## Citation

> US National Institutes of Health, RePORTER application 9932341, Therapeutic targeting of growth factor receptors to treat Mucormycosis (5R01AI141360-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932341. Licensed CC0.

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