# Embryonic Stem Cell Therapy after Cervical Contusion SCI in NHPs

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $686,723

## Abstract

This new application represents a continuation of the California Primate Spinal Cord Research
Consortium project on human embryonic stem cell (hESC) derived neural stem cell
transplantation; our overarching goal is to understand both basic mechanisms of spinal cord
organization and function in non-human primates, and to leverage these and other advances in
developing translational human pro-regenerative therapies. We have made considerable
progress in the last 5 years and now propose new specific aims that will directly bear on the
potential of human neural stem cells (NSCs) to benefit human SCI.
Aim 1: Examine Mechanisms Underlying Graft-Related Functional Improvement: Graft
Silencing with Inhibitory DREADDs. Work in this aim will establish whether functional
recovery observed in non-human primates after grafts of spinalized neural stem cells is related
to graft activation of host neural circuits. This knowledge will be important for human translation.
Aim 2: Determine Whether 4-AP Improves Anatomical and Functional Outcomes After
Neural Stem Cell Grafts There is a vast literature supporting potentially beneficial effects of
4AP in SCI, and 4AP is approved for human use as a conduction-enhancing drug in multiple
sclerosis. This aim will determine whether treatment with neural stem cell grafts plus 4AP
improves anatomical and functional outcomes.
Aim 3: Determine Whether PTEN/SOCS3 Inhibition Improves Host Corticospinal
Regeneration and Functional Outcomes. Rodent studies indicate that functional benefits of
neural stem cell grafts are mediated by formation of host-to-graft-to-host electrophysiological
relays across sites of SCI. These relays require host axon regeneration into grafts. In humans,
corticospinal axons are essential for voluntary movement. This aim will determine whether
inactivation of PTEN/SOCS3 will enhance corticospinal axon regeneration and improve
functional outcomes in primates.

## Key facts

- **NIH application ID:** 10568090
- **Project number:** 1R01NS130033-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JACQUELINE C BRESNAHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $686,723
- **Award type:** 1
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10568090

## Citation

> US National Institutes of Health, RePORTER application 10568090, Embryonic Stem Cell Therapy after Cervical Contusion SCI in NHPs (1R01NS130033-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10568090. Licensed CC0.

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