# In vivo reprogramming of reactive astrocyte and chemogenetic approach for SCI repair.

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $56,211

## Abstract

Spinal cord injury (SCI) is a devastating event resulting in enormous physical and emotional suffering in
patients. SCI patients often live with paralysis and extremely reduced quality of life and productivity.
Therapeutic intervention(s) to restore even partial function would significantly increase the quality of life for
those patients. Axonal degeneration significantly contributes to functional loss after SCI. Unfortunately, axons
in the adult mammalian CNS fail to regenerate after injury due to the non-permissive environment formed
primarily by astroglial scars. Astroglial scars not only form a physical barrier, but they also secrete inhibitors,
such as chondroitin sulfate proteoglycans (CSPGs), to inhibit the regrowth of injured axons. Previous studies
show that degradation of CSPGs, or application of its antagonists, can promote axonal regeneration after SCI.
However, these methods only temporarily remove the inhibitory CSPG and are very limited in promoting axonal
regeneration and functional recovery after SCI. In this study, we will use novel genetic methods to permanently
change the fate of astroglial scars to enhance self-repair of axons after SCI. We hypothesize that in vivo
reprogramming of the inhibitory reactive astrocytes into neurons will promote functional recovery after SCI by
two synergistic mechanisms: 1) decreasing the astrogliosis and its inhibition to promote regeneration of
descending motor tracts; and 2) forming neuronal relay reconnecting the injured descending axons and its
caudal target neurons. We will test these hypotheses using three specific aims. Aim 1 will examine in vivo
reprogramming of reactive astrocytes after SCI. We hypothesize that forced expression of phenotype specific
transcription factors will convert the inhibitory reactive astrocytes into neurons which could integrate into host
circuits. Aim 2 will examine whether in vivo astrocyte reprogramming will promote axonal regeneration and
functional recovery after SCI. Aim 3 will examine whether combination of in vivo astrocyte reprogramming with
multineurotrophin D15A will further promote axonal regeneration and functional recovery after chronic SCI. The
proposed studies will help us evaluate the therapeutic potential of in vivo astrocyte reprogramming after SCI
and understand the mechanisms of this novel approach for functional recovery. These studies could help us
develop the much-needed novel effective therapies for SCI.

## Key facts

- **NIH application ID:** 10176608
- **Project number:** 5R01NS099635-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** QI LIN CAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $56,211
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176608

## Citation

> US National Institutes of Health, RePORTER application 10176608, In vivo reprogramming of reactive astrocyte and chemogenetic approach for SCI repair. (5R01NS099635-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176608. Licensed CC0.

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