# Genome-Wide Discovery and Translational Research for Neural Repair

> **NIH NIH R35** · YALE UNIVERSITY · 2023 · $1,044,835

## Abstract

SUMMARY
Devastating and persistent neurological deficits occur after Spinal Cord Injury (SCI), despite survival of nearly
all neurons. The primary cause of disability is disconnection of networks by axon transection. Recovery of
some movement would be adequate for patients to gain a level of independence in wheel chair transfers,
bowel and bladder management, and locomotion. Today, there is no approved medical therapy for the 300,000
to 1,200,000 individuals in the USA with SCI.
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. Our axonal growth studies
included discovery of Nogo and Nogo Receptor (NgR1). We demonstrated their role in preventing axonal
sprouting, regeneration and recovery after injury. We have demonstrated that NgR1(310)-Fc is efficacious for
recovery from SCI, even when treatment starts months after damage. It is being developed for human SCI
trials now.
While specific factors, such as NgR1, limiting axon regeneration have been identified, they provide an
incomplete explanation for poor adult mammalian CNS regeneration. We completed a genome-wide shRNA
screen for endogenous genes limiting mammalian CNS axon repair. The validity of this method was
demonstrated by the identification of INPP5F as a gene limiting neural repair in a pilot screen of phosphatases.
One cellular pathway is bioinformatically the most enriched gene set in the mammalian screen, and also
regulates regeneration in nematodes. The relevance of this pathway will be tested in preclinical models of
traumatic SCI. Both gene deletion strains and pharmacological inhibition will be studied to provide a validated
pathway for future therapeutic development. The findings will have high relevance for the development of novel
therapeutics for SCI.

## Key facts

- **NIH application ID:** 10528486
- **Project number:** 5R35NS097283-07
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** STEPHEN M STRITTMATTER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,044,835
- **Award type:** 5
- **Project period:** 2016-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528486

## Citation

> US National Institutes of Health, RePORTER application 10528486, Genome-Wide Discovery and Translational Research for Neural Repair (5R35NS097283-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10528486. Licensed CC0.

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