# NIH grant: A Dual Nitric Oxide Donor for Sickle Cell Disease Associated Acute Chest Syndrome (1R44HL186981-01) — retained record

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[original source ↗](https://reporter.nih.gov/project-details/1R44HL186981-01)

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NIH grant 1R44HL186981-01: A Dual Nitric Oxide Donor for Sickle Cell Disease Associated Acute Chest Syndrome
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Kathryn W Woodburn. Award: $1331241.
Start: 2026-09-05T00:00:00.
Public Abstract
Acute chest syndrome (ACS) is a leading cause of hospitalization and death in individuals with sickle cell disease
(SCD), yet no approved therapy directly targets its underlying pathophysiology. Current care focuses on
preventing respiratory failure and mitigating irreversible lung damage through supportive interventions such as
pain control, fluid resuscitation, supplemental oxygen, blood transfusion, antibiotic therapy, and
thromboembolism prophylaxis. While essential, these measures do not address the underlying pathophysiology,
specifically the dysregulation of nitric oxide (NO) signaling
DIMERx is developing DMX-201, 2-amino-5-guanidino-N-(4-guanidinobutyl)pentanamide, a novel L-arginine-
agmatine conjugate and high-density NO donor designed to generate sustained NO production while
circumventing toxicity associated with current NO systems. DMX-201 has demonstrated safety and biological
activity in human microvascular endothelial cells. In nonhuman primates, it is well tolerated and exhibits a
sustained-release pharmacokinetic profile following intravenous administration.
This proposal aims to further evaluate the safety and therapeutic activity of DMX-201 in a clinically relevant
murine model of SCD-associated ACS. Additional studies will assess red blood cell adhesion and occlusion
using samples from SCD patients and conduct single- and repeat-dose rodent studies to inform dosing for future
Investigational New Drug (IND)-enabling studies required by U.S. Food and Drug Administration (FDA).
If these findings translate clinically, DMX-201 has the potential to become a first-line therapeutic for the treatment
for ACS in SCD, offering a durable, mechanism-based alternative to current supportive care. This could lead to
reduced frequency of vaso-occlusive crises, shortened hospital stays, decreased opioid use, and improved
quality of life for affected individuals and their families.
```



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