# Evaluation of Novel Axon Regeneration Targets for Spinal Cord injury Therapy

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $253,571

## Abstract

SUMMARY
The CNS of adult mammals, as compared to the peripheral nervous system of mammals or the nervous
system of other organisms, has extremely limited capacity for axonal regeneration. Specific factors limiting
adult mammalian regeneration of axons have been identified, but they provide an incomplete explanation for
poor adult mammalian CNS regeneration. We have completed a genome-wide shRNA-based screen for
endogenous genes limiting the repair of axons in the mammalian CNS. We have also conducted experiments
to identify conserved genes that affect axon regeneration in the model organism C. elegans. Factors common
to both experimental systems are expected to identify fundamental mechanisms in regeneration that
are likely to affect the equivalent process in human patients. We aim to study and develop the
translational potential of those evolutionarily conserved mechanisms here.
From our studies we have selected one evolutionarily conserved pathway identified both in mouse cell culture
and in C. elegans axon regeneration. It is bioinformatically the most enriched gene set in the primary
mammalian screen data, with multiple family members identified, and also regulates regeneration in C. elegans.
The relevance of the pathway will be tested in preclinical models of traumatic spinal cord injury. Multiple steps
in the pathway will be assessed in rodent spinal cord injury models. Both gene deletion strains and
pharmacological inhibition will be studied to provide a validated pathway for future therapeutic development.
While we will focus on one particular pathway regulating membrane traffic in the axon, we will utilize both laser
axotomy and mouse spinal cord traumatic injury to explore additional pathways identified in the primary screen.
This project builds on genetic screens in the mature mammalian central nervous system and C. elegans to
analyze novel mechanisms that promote axon regeneration after mammalian spinal cord injury. The findings
will have high relevance for the development of novel therapeutics for neurological disorders.

## Key facts

- **NIH application ID:** 9968465
- **Project number:** 5R01NS098817-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MARC HAMMARLUND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $253,571
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968465

## Citation

> US National Institutes of Health, RePORTER application 9968465, Evaluation of Novel Axon Regeneration Targets for Spinal Cord injury Therapy (5R01NS098817-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968465. Licensed CC0.

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