# GPR39 as a Therapeutic Target in Subarachnoid Hemorrhage (SAH)

> **NIH NIH R41** · NEUVARX, LLC · 2022 · $251,946

## Abstract

TITLE: GPR39 as a Therapeutic Target in Subarachnoid Hemorrhage (SAH)
Summary Abstract
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke that affects 20-30,000 patients
in the US every year, killing between a third and a half of its victims. Worldwide, SAH is responsible for more
than 400,000 deaths each year. There is currently no effective treatment for SAH beyond the initial surgical
or endovascular intervention to stop the bleed. However, most deaths occur after the initial bleed, due to
early brain injury (EBI) or delayed cerebral ischemia (DCI). We propose to develop a first-in-class small
molecule drug that targets a novel GPCR (GPR39) that is relevant to both
EBI
and DCI. In support of the
relevance of this pathway to SAH, we have recently completed a Phase 1b randomized clinical trial in SAH
patients using a compound that increases the endogenous level of the natural ligand for this receptor (called
14,15-epoxyeicosatrienoate, 14,15-EET). In the clinical trial, increasing 14,15-EET (by inhibiting its
breakdown) reduced hospital stay from 29 days to 17 days, and improved functional outcome at 90 days
after SAH from severe to moderate disability and from moderate to slight disability. We have recently
discovered GPR39 as the receptor for 14,15-EET, which raises the opportunity to stimulate the receptor
directly, rather than indirectly by increasing its ligand. To that end, we have completed high-throughput
screening (HTS) of a small-molecule library containing more than 250,000 molecules that identified several
promising compounds with high selectivity, potency and drug-like properties. The goal of this Phase I STTR
is to confirm the role of GPR39 in SAH using GPR39 knockout mice and a publically available GPR39 agonist,
called C3, developed by others for other indications. Studies will use 3- and 12-month old male and female
mice. Studies will also determine C3 plasma PK for C3, and whether it penetrates the blood-brain barrier
(BBB). Future Phase II STTR will support a hit-to-lead medicinal-chemistry campaign aimed at identifying a
lead compound with high in-vitro potency, in-vivo efficacy, and favorable PK/PD properties, including blood-
brain barrier penetration.

## Key facts

- **NIH application ID:** 10478533
- **Project number:** 1R41NS127634-01
- **Recipient organization:** NEUVARX, LLC
- **Principal Investigator:** Nabil J Alkayed
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $251,946
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478533

## Citation

> US National Institutes of Health, RePORTER application 10478533, GPR39 as a Therapeutic Target in Subarachnoid Hemorrhage (SAH) (1R41NS127634-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478533. Licensed CC0.

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