# Promoting axon regeneration and functional recovery after SCI

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $387,188

## Abstract

PROJECT SUMMARY
Spinal cord injury (SCI) results in the loss of voluntary control of the body part below the injury site. Severed
connection between the brain neurons with long-projecting descending axons and the spinal circuits below the
lesion is one main cause of such paralysis. Thus, promoting transected axons to regenerate across lesion
represents the most ideal strategy for re-building circuits and restoring functions. However, these adult
descending axons are regeneration-refractory. Recent studies suggested that a key reason for their
regeneration failure is the diminished intrinsic regenerative capacity after injury in adult. In this regard, we and
others showed that deletion of PTEN, a negative regulator of mTOR, in either young or adult corticospinal
neurons is able to activates their intrinsic regenerative ability, resulting in robust re-growth of transected
corticospinal tract (CST) axons. While providing new venues of enabling injured CST axons to mount a
regenerative response, these results raise several challenges towards translating these findings to a possible
therapeutic strategy. First, while PTEN deletion in cortical neurons resulted in significant CST regrowth,
achieving robust and long-distance regeneration for functional recovery might need further optimization of the
intrinsic regenerative ability of these mature corticospinal neurons. Second, considering the importance of
other descending tracts (in addition to CST), it is important to assess whether their regenerations are also
regulated by such manipulations. Third, While PTEN inhibition provides a valuable manipulation for proof-of-
principle studies, the biological nature of PTEN as a tumor suppressor raises safety concerns for its clinical
application. Thus, it is crucial to develop other safe methods of mimicking the effects of PTEN inhibition in
activating mTOR and promoting axon regeneration and functional recovery. The proposed studies in this
application will extend our recent exciting findings to address each of these issues, in a hope to develop
clinically relevant neural repair strategies for spinal cord injury.

## Key facts

- **NIH application ID:** 9972962
- **Project number:** 5R01NS096294-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ZHIGANG HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,188
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972962

## Citation

> US National Institutes of Health, RePORTER application 9972962, Promoting axon regeneration and functional recovery after SCI (5R01NS096294-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972962. Licensed CC0.

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