# An additive solution to expand the lung transplant organ pool

> **NIH NIH R41** · PEROXITECH, LLC · 2022 · $299,931

## Abstract

PROJECT SUMMARY
Major challenges in the field of lung transplantation are the low availability of healthy donor lungs (graft) and
the damage to donor lungs post-transplant. These arise due to inflammation and oxidative damage initiated
during the graft storage period. Among the multiple strategies employed to improve lung availability and
transplant outcome are short storage times (comprising of < 3 h, storage under perfusion i.e. ex vivo lung
perfusion or EVLP circuit, hypothermic storage, and the use of various antioxidant solutions) and
immunosuppression therapy post-transplant. Of these, EVLP alone shows promise; however it is cost-
prohibitive and often unavailable at the point of site of lung procurement. Immunosuppressive therapy, though
partially effective is debilitating for the transplant recipient.
Peroxitech LLC proposes to use an alternate strategy of blocking the earliest signaling events that are
triggered during lung storage and that in turn lead to inflammation and injury. Work from the Chatterjee group
has shown that pulmonary vascular wall responds to stop of blood flow associated with lung storage by
activating an endothelial signaling cascade that leads to activation of NADPH oxidase 2 (NOX2) and reactive
oxygen species (ROS) production. This group also reported that the phospholipase A2 (PLA2) activity of the
enzyme Peroxiredoxin 6 is crucial in NOX2 activation. Recently, Peroxitech discovered a nine amino-acid
peptide sequence (PIP-2) that can block the PLA2 activity of Prdx6 and thus diminish NOX2 activation and
ROS production. Preliminary data shows that murine lungs stored in the 9 peptide aminoacid significantly
reduced ROS production. ROS generation in lungs is well established to cause activation of inflammation and
antigen presentation cascades which are signals for recruitment of innate (polymorphonuclear neutrophils or
PMN) and adaptive immune cells (T lymphocytes) from the recipient. PMN adhere to the vessel wall of the
newly transplanted lung (graft), transmigrate and release oxidants causing injury to the graft while activated T-
lymphocytes drive lysis of the graft tissue. Peroxitech proposes to pre-“treat” donor lungs by blocking the
signals during storage with PIP-2 (outside the body) such that PMN recruitment and T cell activation (both of
which are ROS dependent) after transplant, is minimized. For this will evaluate PIP-2 as a lung preservation
solution. We will in Aim 1) Evaluate PIP-2 formulations for effectivity in donor lung protection with increasing
storage times and Aim 2) Evaluate the effect of PIP-2 as a preservation solution in murine lung transplant
outcomes. If data obtained show that PIP-2 usage during lung storage leads to a significant reduction in
inflammation, injury and an improved lung function, post-transplant, we will be enabled to proceed to Phase II
with a full clinical and analytical evaluation of this agent in isolated human donor lungs, for an eventual FDA
approval.

## Key facts

- **NIH application ID:** 10480375
- **Project number:** 1R41HL164161-01
- **Recipient organization:** PEROXITECH, LLC
- **Principal Investigator:** SHAMPA CHATTERJEE
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $299,931
- **Award type:** 1
- **Project period:** 2022-04-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480375

## Citation

> US National Institutes of Health, RePORTER application 10480375, An additive solution to expand the lung transplant organ pool (1R41HL164161-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10480375. Licensed CC0.

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