# Treatment of diabetic retinopathy with TrkB agonist antibodies

> **NIH NIH R41** · ZEBRA BIOLOGICS, INC. · 2020 · $210,578

## Abstract

Project Summary/Abstract
 Diabetic retinopathy (DR) is a major co-morbidity for patients with Type 1 and Type 2 diabetes. The
incidence and severity of DR increase with duration of diabetes and approximately 30 percent will experience
vision-threatening deficits. Work over the past decade has shown that the neural deficits observed in DR occur
early in the natural history of the disease and likely precede vascular pathology, shifting a focus of research
and drug discovery toward restoring function of retinal neurons. The overall goal of this Phase I STTR grant
proposal is to establish proof-of-concept efficacy of a TrkB agonist antibody, ZEB85, in experimental DR and to
provide a path for preclinical development, clinical trials and ultimately commercialization of these novel
therapeutics for the treatment of DR, a critical medical need.
 In Specific Aim (SA) 1 we will determine Localization and target engagement of TrkB agonist antibodies
delivered to the eye. Upon intravitreal (ivt) delivery of TrkB agonist antibody, ZEB85, we will determine its
localization to TrkB-expressing retinal ganglion cells (RGCs), and establish target engagement by measuring
phospho-TrkB, both by immuinohistological methds. We will also determine whether repeated ivt injections of
TrkB agonist antibody induce desensitization of TrkB signaling in the retina. These localization and target
engagement validation studies are critical for interpretation of ZEB85 efficacy studies in a rat model of DR,
planned in SA2.
 In SA2 we will determine the ability of TrkB agonist antibody ZEB85 to ameliorate the antomical and
functional deficits in streptozotocin (STZ)-induced DR. We will assess dose-dependent restoration of
pattern ERG deficits, retinal neuron apoptosis and RGC synaptic markers after 12 weeks of ZEB85 treatment
in rats with DR. These studies will demonstrate dose-dependent efficacy of TrkB agonist antibody treatment for
DR.
 Successful achievement of these Milestones will provide a foundation to examine ZEB85 distribution and
target engagement in a larger mammalian eye (e.g., rabbit, monkey, human), and assess its pharmacology
and safety in anticipation of IND-enabling studies, eventual clinical trials and commercialization.
 Long term, we propose that ivt treatment with TrkB agonist antibodies is a novel approach that can
complement current standard-of-care therapy for DR, allowing eventual clinical trials to be run concurrently
with anti-VEGF therapy, with the goal of identifying additive or synergistic efficacy for DR patients.

## Key facts

- **NIH application ID:** 10079993
- **Project number:** 1R41EY032011-01
- **Recipient organization:** ZEBRA BIOLOGICS, INC.
- **Principal Investigator:** PETER S DISTEFANO
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $210,578
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079993

## Citation

> US National Institutes of Health, RePORTER application 10079993, Treatment of diabetic retinopathy with TrkB agonist antibodies (1R41EY032011-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10079993. Licensed CC0.

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