# Develop a combinatorial therapy for spinal cord injury

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $342,890

## Abstract

Project Summary
Severed CNS axons fail to regenerate largely because of the reduced intrinsic growth capacity of adult
neurons and poor environment for axon extension. The Co-I's Lab finds that the Wnt family molecules and their
receptors are upregulated after spinal cord injury (SCI) and mediates regrowth
Among
adult
failure of injured fiber tracts.
several Wnt receptors, Ryk is crucial for mediating repulsive axon growth during development and in
CNS after injury.Chondroitin sulfate proteoglycans (CSPGs) generated by glial scars strongly suppress
axon extension and are major extrinsic molecular targets for treating CNS injury. The PI's group designed
small peptides to block functions of CSPG receptors LAR and PTPσ by targeting their critical activity domains
and demonstrated their high efficiency for promoting axon growth. Blocking each of the two receptors with 3
combined peptides promotes robust regeneration of injured CNS axons. We hypothesize that inhibiting both
Wnt and CSPG signals represents a dual approach of enhancing neuronal growth capacity and reducing
environmental inhibitory influence at the lesion site. We propose to stimulate robust axon regrowth in adult
rodents with transection or contusion SCI by inhibiting Ryk and LAR/PTPσ with genetic and pharmacological
approaches available in our labs. In Aim 1, we will study synergistic actions of transgenically deleting Ryk plus
each of LAR/PTPσ receptors on promoting axon regeneration and recovery in mice with SCI. We will
determine whether deleting Ryk plus LAR or Ryk plus PTPσ receptors acts synergistically to stimulate axon
growth and enhance neuronal plasticity in double knockout mice after SCI. In Aim 2, we will determine whether
blocking each of Ryk, LAR and PTPσ receptors with antibody or selective antagonists pharmacologically
promotes axon regeneration and recovery in adult rats with SCI. We will compare effectiveness of the
treatments that target individual receptors in promoting regrowth of multiple descending tracts and recovery of
locomotor functions after SCI. In Aim 3, we will study whether combination therapies that block two or three
receptors yield better axon regrowth and functional recovery in rats with transection or contusion SCI, aiming to
identify the optimal therapy for mammals with SCI. Based on the promising results from our pilot studies, we
predict that our combined strategies will promote dramatic regeneration of injured axon tracts and recovery of
locomotion function in vivo. Our novel strategy of administering deliverable compounds post-injury may
facilitate development of a practical combinatorial therapy for CNS lesions.

## Key facts

- **NIH application ID:** 9948779
- **Project number:** 5R01NS105961-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** SHUXIN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,890
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948779

## Citation

> US National Institutes of Health, RePORTER application 9948779, Develop a combinatorial therapy for spinal cord injury (5R01NS105961-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948779. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*