# A selective angiogenesis blocker to treat retinopathy of prematurity

> **NIH NIH R24** · BAYLOR COLLEGE OF MEDICINE · 2022 · $76,000

## Abstract

Project Summary
Retinopathy of prematurity (ROP) is a leading cause of vision loss in children and is currently treated by laser
therapy or cryotherapy. However, both treatments destroy the peripheral vision to save the central vision with
limited efficacy and do not address the underlying cause of pathological retinal neovascularization. There is no
approved drug therapy for ROP in the U.S. Because vascular endothelial growth factor (VEGF) is critical to
both physiological and pathological angiogenesis in ROP retinas, anti-VEGF therapy interferes with
vasculogenesis and retinogenesis in premature infants, leading to adverse effects. As a result, VEGF inhibitors
have safety concerns for ROP therapy. To address this urgent unmet clinical need, we recently discovered
secretogranin III (Scg3) as a highly disease-restricted pro-angiogenic factor that preferentially binds to and
stimulates angiogenesis of diseased but not normal vessels. This is in contrast to VEGF which indiscriminately
binds to and induces angiogenesis of both diseased and normal vessels. We further developed anti-Scg3 mAbs
and humanized antibodies (hAbs) to selectively inhibit pathological but not physiological angiogenesis. The
critical barrier for the translation of anti-Scg3 therapy is the unknown clinical relevance of Scg3 to ROP. One of
the approaches to define the clinical relevance is to identify the unknown Scg3 receptor (Scg3R) and characterize
its upregulation on ROP vessels. We hypothesize that Scg3 is a clinically relevant angiogenic factor to ROP
because of the marked upregulation of Scg3R in the disease condition. In Aim 1, we will use a new technique to
screen and identify Scg3R. In Aim 2, we will verify Scg3R and its specific interaction with Scg3. In Aim 3, we will
confirm Scg3R upregulation on ROP vs. healthy retinal vessels. The successful implementation of this project
will unravel the first disease-selective ligand-receptor pair to exclusively regulate pathological but not
physiological angiogenesis. Identification of Scg3R and validation of its upregulation on ROP vessels will
unambiguously support the clinical relevance of anti-Scg3 therapy and facilitate the clinical translation of anti-
Scg3 hAbs.

## Key facts

- **NIH application ID:** 10580497
- **Project number:** 3R24EY028764-04S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Wei Li
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $76,000
- **Award type:** 3
- **Project period:** 2019-02-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580497

## Citation

> US National Institutes of Health, RePORTER application 10580497, A selective angiogenesis blocker to treat retinopathy of prematurity (3R24EY028764-04S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10580497. Licensed CC0.

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