Related Experiment Video
Updated: Aug 11, 2026
Lumbar Intrathecal Injection of Gene Therapy Vectors for Central Nervous System Targeting in Mice and Rats
Published on: May 16, 2025
Safety assessment of intradiscal gene transfer: a pilot study
Corey J Wallach1, Joseph S Kim, Satoshi Sobajima
1Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, C313-PUH, PA 15213, USA.
Background:
Several recent in vitro and in vivo studies have reported the beneficial properties of gene delivery of therapeutic factors to the intervertebral disc, as a potential treatment strategy for degenerative disc disease; however, to date, no studies have assessed the safety and toxicity of the practical application of this treatment modality.
Purpose:
To assess the safety of inappropriately dosed or misdirected gene delivery to the spinal column in an in vivo model.
Study Design:
The potential toxicity of gene therapy to the spinal column was assessed in this pilot study by monitoring clinical and histological changes in the spinal cord after intradural injections of an adenoviral vector containing the complementary deoxyribonucleic acid (cDNA) for potentially therapeutic factors in the treatment of degenerative disc disease.
Methods:
Fourteen New Zealand White rabbits were divided into experimental groups to receive an intradural injection (<10 microL) of saline alone or saline in combination with recombinant transforming growth factor beta1 (TGF-beta1) or an adenoviral vector containing the cDNA for either TGF-beta1 (at previously established therapeutic or elevated concentrations) or bone morphogenic protein-2 (BMP-2). Animals were monitored clinically and spinal cords were harvested for histological analysis.
Results:
No neurological deficits developed in any of the animals receiving injections of saline alone or saline in combination with the therapeutic dose of Ad-TGF-beta1, Ad-BMP-2, or with recombinant TGF-beta1. However, animals receiving a higher concentration of Ad-TGF-beta1 developed bilateral lower extremity paralysis with significant histological changes.
Conclusions:
Inappropriately dosed or directed gene delivery to the spinal column may result in significant complications. However, with appropriate dosing, a therapeutic window may exist where the potential benefits of gene therapy in the treatment of degenerative disc disease outweigh its risks.
