# Improving marginal allograft outcomes through cell junction stabilization in transplantation

> **NIH NIH R44** · XEQUEL BIO, INC. · 2022 · $987,481

## Abstract

Project Summary/Abstract: Transplantation is a highly successful therapy for end-stage renal disease but there
is a significant shortage of available donor organs that has forced utilization of low-quality kidneys to save
patient’s lives. Extending the donor criteria has coincided with a growing appreciate that factors associated with
organ donation, procurement and storage greatly affect post-transplantation outcomes. Unlike heart
transplantation, kidney donors can be derived from a variety of sources that include living donors, donation after
brain death, and donation after cardiac death. However, the vast majority of kidneys are donated from deceased
donors and donation after brain death or after cardiac death predispose poorer post-transplantation outcomes.
Problems inherent to organ transplantation, such as ischemia and extended cold storage, also negatively affect
and cause irreparable damage to the donor kidney. These injurious events are known to elicit endothelial cell
(EC) dysfunction, inflammation, and organ injury that are further exacerbated upon implantation by ischemia
reperfusion injury (IRI) while also priming the donor organ for alloimmune recognition. While cold preservation
has greatly facilitated the use of cadaveric kidneys for transplantation by slowing metabolism to prevent cell
death, current formulations do not minimize organ injury associated with cold storage or ischemia reperfusion
injury. Vascular endothelum, which serves as a dynamic interface between the allograft and the recipient, is the
initial target of the deleterious events that adversely affect graft health and function. Since gap and tight junctions
regulate EC functionality, therapeutic strategies that promote the molecular and cellular integrity of endothelium
of donor kidneys could preclude the mechanisms responsible for allograft damage and failure. FirstString
Research Inc. has identified, characterized, and clinically-evaluated a novel peptide mimetic of connexin43,
alpha-Connexin Carboxy-Terminal (aCT1), that stabilizes the gap and tight junctions of ECs during wound
healing processes, leading to coordination of cellular communication, dampened inflammatory responses,
reduced immune cell infiltrate, and enhanced regenerative properties. aCT1’s small, stable, soluble design
facilitates direct translocation into cells for intracellular drug delivery. Preliminary studies in clinically relevant
models of kidney, heart, and lung transplantation reveal that aCT1 supplementation to standard-of-care organ
preservation solutions stabilizes cellular junctions to protect EC from injurious effects of IRI and extending cold
storage time. We hypothesize that cold preservation induces cell junction damage, which leads to EC
dysfunction, inflammation, and renal damage upon reperfusion, and that supplementation of the
therapeutic aCT1 peptide to standard of care preservation solution will preserve cell junctions, thereby
improving renal health and function leading to...

## Key facts

- **NIH application ID:** 10436958
- **Project number:** 5R44DK125244-03
- **Recipient organization:** XEQUEL BIO, INC.
- **Principal Investigator:** Christina Grek
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $987,481
- **Award type:** 5
- **Project period:** 2020-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436958

## Citation

> US National Institutes of Health, RePORTER application 10436958, Improving marginal allograft outcomes through cell junction stabilization in transplantation (5R44DK125244-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436958. Licensed CC0.

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