# An exercise surrogate to enhance recovery following repair of peripheral nerve injuries

> **NIH NIH R03** · EMORY UNIVERSITY · 2020 · $156,000

## Abstract

Project summary/Abstract
Peripheral nerve injuries are common with more than 200,000 new cases reported each year in the United States alone.
Only about 10% of these individuals regain much function. Nerve injuries significantly impact the long-term quality of
life, and many injured individuals seek continued life-long treatments for associated disabilities and pain. The common
reason given for the poor functional outcomes is the process of axon regeneration. Over the past decade, our laboratory
has shown that exercise strikingly enhances peripheral axon regeneration and significantly improves functional recovery
following complete nerve. However, the translational potential of exercise has limitations. Many patients are not
candidates for exercise due to issues, such as co-morbidities that preclude rehabilitation, necessary immobilization of a
limb following surgical nerve repair, unknown dose requirement of exercise and patient compliance. We propose here a
novel therapy for peripheral nerve injury that exploits a downstream effector of exercise (hypoxia inducible factor 1,
HIF1) to promote sensory and motor axon regeneration in a non-invasive manner, and in a way that could be utilized by
all nerve injury patients.
Based on the literature, we suggest that HIF1α may be the key mediator of how exercise robustly promotes axon
regeneration after nerve injury. The HIF complex controls the transcription of numerous genes associated with
neurogenesis, neuronal survival, neuronal metabolism, and angiogenesis. De-regulation of HIF1α has been identified in
several neurodegenerative diseases (e.g., amyotrophic lateral sclerosis) and neural injuries (e.g., spinal cord injury and
stroke). Notably, neuronal HIF1α was shown to be required for axon regeneration after peripheral nerve injury.
With pilot data, we show that the exercise protocol we have shown to enhance axon regeneration after sciatic nerve
injury upregulates HIF1α in axotomized motoneurons. We also show that by pharmacologically stabilizing HIF1α, axons
elongated even farther than after treatment with exercise. The goal of this study will be to investigate the fundamentals
of pharmacologically stabilizing HIF1α in axotomized motor and sensory neurons to treat peripheral nerve injuries in
males and females. Our proposed pharmacologic approach has been safely used long-term in humans, so that this
approach would be practical to translate to human studies.

## Key facts

- **NIH application ID:** 9857058
- **Project number:** 5R03HD097737-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Patricia Jill Ward
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,000
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857058

## Citation

> US National Institutes of Health, RePORTER application 9857058, An exercise surrogate to enhance recovery following repair of peripheral nerve injuries (5R03HD097737-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857058. Licensed CC0.

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