# Complement C5 inhibition as sepsis therapy

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2022 · $633,416

## Abstract

PROJECT SUMMARY
Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Sepsis is a
leading cause of death in intensive care units. The contact of pathogens with the intravascular compartment of
the host leads to systemic inflammation, wherein activation of the complement and coagulation systems plays
critical roles.
The objectives of this proposal are to investigate the role of complement activation and its crosstalk with
inflammation and coagulation to sepsis progression and multiple organ failure (MOF) and, whether blocking
complement activation at the C5 level could prevent MOF and improve the outcome of sepsis.
We will use clinically relevant models of sepsis caused by two of the most common pathogens, Escherichia coli
and Staphylococcus aureus to: (i) determine the contribution of complement and coagulation to pathogenesis
of microthrombosis, vascular dysfunction, organ failure and death; (ii) test stage-specific therapies targeting the
complement and coagulation cascades to provide organ protection and survival benefit in sepsis-induced
progressive MOF.
Successful completion of these aims will determine: (i) whether timed complement inhibition at the C5 level
could be used as an effective therapy for sepsis-induced MOF; (ii) if inhibition of C5a receptor-1 signaling could
attenuate disease progression and provide organ protection; (iii) if combination therapies employing early
treatment with an anticoagulant and a delayed treatment with a C5 inhibitor will provide synergistic protection
in cases of high septic bacteremia/shock.
Altogether, our project will combine basic and preclinical research to verify novel hypotheses on the
pathophysiology of both Gram-negative and Gram-positive sepsis, and test innovative approaches, which in
the long-term may save lives from this deadly disease with no specific cure.

## Key facts

- **NIH application ID:** 10420351
- **Project number:** 1R01AI168355-01
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** FLOREA LUPU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $633,416
- **Award type:** 1
- **Project period:** 2022-02-09 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10420351

## Citation

> US National Institutes of Health, RePORTER application 10420351, Complement C5 inhibition as sepsis therapy (1R01AI168355-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10420351. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*