# SCI Consortium Study: Enhancing Corticospinal Tract Axonal Regeneration After Spinal Cord Injury

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

Project Summary
Corticospinal tract (CST) is an important supraspinal descending motor system that
controls voluntary movement in humans. Good progress has been made in recent years
to elicit CST axonal regeneration and re-connectivity after spinal cord injury (SCI). For
example, conditional deletion of phosphatase and tensin homolog (PTEN) or
pharmacological suppression of PTEN that boosts neuronal intrinsic ability to grow
enhances CST sprouting and regeneration after SCI. Transplantation of neural stem
cells (NSCs) or neural progenitor cells (NPCs) as a permissive extrinsic environment
supports extensive CST regeneration into SCI/transplant site. These exciting results
provide an unprecedented opportunity that is the subject of this grant: combine NSC
grafts with pharmacological suppression of PTEN to generate the most extensive CST
regeneration described to date. In a logical extension of this work related to the VA's
rehabilitation mission, we will combine rehabilitation training, hypothesizing that this will
re-shape and strengthen connectivity of regenerating CST axons to further enhance
functional recovery.
There are 3 Aims in the proposed studies. The specific Aim 1 is to determine whether
combined NPC grafts and pharmacological PTEN suppression promote CST
regeneration and skilled forelimb functional recovery. The specific Aim 2 is to determine
whether combined NPC transplants and skilled forelimb reach rehabilitation training
enhance CST regeneration and forelimb functional recovery. Last, the specific Aim 3 is
to determine whether combined NPC transplants, pharmacological PTEN suppression,
and skilled forelimb reach rehabilitation training optimize CST regeneration and forelimb
functional recovery. All these Aims are based on previous reports and supported by our
preliminary feasibility data. Findings of this work will substantially extend our knowledge
of NPC/NSC treatments for SCI, in a systematic set of experiments designed to be
translationally relevant and specifically focused on interventions for Veterans.

## Key facts

- **NIH application ID:** 9995389
- **Project number:** 5I01RX002264-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Pengzhe Lu
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995389

## Citation

> US National Institutes of Health, RePORTER application 9995389, SCI Consortium Study: Enhancing Corticospinal Tract Axonal Regeneration After Spinal Cord Injury (5I01RX002264-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9995389. Licensed CC0.

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