# Intervertebral Disc Degeneration and Cross-Talk with the Nervous System

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $56,155

## Abstract

Intervertebral disc (IVD) degeneration is one of the greatest contributors to low back pain, yet how the IVD can
generate pain remains poorly understood. The parent grant will pursue Specific Aims to study the development
of temporal and spatial changes in neuronal function and their “cross-talk” with changes in the degenerating IVD
in a mouse model of lumbar IVD degeneration. Here, we propose a supplemental project called “Novel Injectable
Hydrogels for Localized Pain Relief in the Dorsal Root Ganglion (DRG)” that will support Ms. Sydney Neal in the
design of a novel injectable drug depot in order to attenuate neuronal sensitivity with lumbar IVD degeneration.
 The overall goal is for Ms. Neal, a graduate student in biomedical engineering, to develop a novel
chemistry that will couple the nerve growth factor (NGF) antagonist, Tanuzemab, to an injectable, gelling alginate
to provide for local release of an NGF antagonist at the lumbar DRGs with IVD degeneration. In Supplemental
Aim 1, Ms. Neal will modify binary mixtures of alginate and evaluate gelation kinetics and localization to the
DRGs following simulated perineural delivery. In Supplemental Aim 2, Ms. Neal will develop a strategy to
couple Tanezumab to alginate using an azide modification and evaluate the efficiency of coupling. In
Supplemental Aim 3, Ms. Neal will evaluate the bioactivity of the drug-conjugated alginate hydrogels in isolated
DRG neurons subjected to periods of incubation with NGF. Ms. Neal will be co-sponsored by Dr. Nate Huebsch
who brings experience with biomaterials and drug delivery to the team, and Dr. Lori Setton who brings experience
with IVD degeneration and perineural drug delivery to the team.
 During the period of this project, Ms. Neal will gain new and valuable skills in neuronal cell culture,
genetically-encoded calcium indicators, pre-clinical models of disease development, and work closely with
clinicians to increase her knowledge of treatment relevance for engineered biomaterials. Ms. Neal will further
prepare an Individual Development Plan, participate in workshops for research success at Washington
University, attend national conferences to present her work, and have an opportunity to participate in a national
conference to mentor Black scientists. Washington University provides an excellent environment for the
completion of this research project and continued professional development of Ms. Sydney Neal. Ms. Neal will
work within the McKelvey School of Engineering and the School of Medicine and participate in resources of the
Musculoskeletal Research Center, the Cardiovascular Research Center, and the Center for Regenerative
Medicine. In all, these combined research and training activities are designed to prepare Ms. Neal for continued
academic research in her post-graduate years.

## Key facts

- **NIH application ID:** 10412615
- **Project number:** 3R01AR077678-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lori A. Setton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $56,155
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412615

## Citation

> US National Institutes of Health, RePORTER application 10412615, Intervertebral Disc Degeneration and Cross-Talk with the Nervous System (3R01AR077678-02S1). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10412615. Licensed CC0.

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