# Control of intervertebral disc degeneration via matrix-mediated delivery of platelet-derived growth factors

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $423,936

## Abstract

Summary
There is no successful biologic treatment for intervertebral disc degeneration (IDD). The goal of this proposal
is to utilize a hydrogel-based engineering approach to deliver PDGF to intervertebral disc (IVD) tissue and
establish PDGF as a potent inhibitor of IDD. We also aim to define the mechanisms underlying its effects on
normal and diseased nucleus pulposus (NP) and annulus fibrosus (AF) cells using human IVDs as well as
preclinical models of IDD.
The scientific premise for the proposed work is a rigorous body of published evidence demonstrating that PDGF-
BB, as well as PDGF-AB can stimulate disc cell growth and/or inhibit their programmed cell death in vitro. Our
compelling preliminary data in vivo point to an anti-apoptotic effect of PDGF-BB in a rabbit puncture model, which
led to restored disc height and enhanced mechanical properties of the treated discs compared to untreated
controls. It is based on these encouraging data and other molecular preliminary data demonstrating that these
anti-apoptotic effects may be mediated through the transcription factor Runx1, that we postulate the novel
hypothesis that sustained exposure of the NP and AF to PDGF will repress IDD progression through controlling
Runx1 activity.
To test this hypothesis, we will first compare the effects of PDGF-BB and PDGF-AB on normal versus diseased
human AF and NP cells cultured in high density. We will then determine the molecular mechanisms underlying
the anti-degenerative effects of PDGF on disc cells through transcriptomic and functional analyses involving
RUNX1 and other signaling molecules (Aim 1A). The validation of Runx1 function in PDGF-mediated effects will
also be examined in vivo using a new gain of function mouse model (Aim 1B). In the second Aim, we will
fabricate and validate the functionality of an injectable biomaterial capable of sustaining the exposure of disc
cells to PDGF-BB (Aim 2A). We will then establish therapeutic modalities for long-term inhibition of IDD in vivo
by PDGF-BB using a rabbit disc puncture model (Aim 2B). Our proposed work will provide seminal information
about the mechanisms underlying PDGF’s effects on the IVD and the role of Runx1 in IDD. The mechanistic
data will help identify new therapeutic targets to treat IDD.

## Key facts

- **NIH application ID:** 10377961
- **Project number:** 5R01AR076427-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Moulay Hicham DRISSI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,936
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377961

## Citation

> US National Institutes of Health, RePORTER application 10377961, Control of intervertebral disc degeneration via matrix-mediated delivery of platelet-derived growth factors (5R01AR076427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10377961. Licensed CC0.

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