Gene therapy relieves back pain, repairs damaged disc in mice

Disc-related back pain may one day meet its therapeutic match: gene therapy delivered by naturally derived nanocarriers that, a new study shows, repairs damaged discs in the spine and lowers pain symptoms in mice.

Scientists engineered nanocarriers using mouse connective-tissue cells called fibroblasts as a model of skin cells and loaded them with genetic material for a protein key to tissue development. The team injected a solution containing the carriers into damaged discs in mice at the same time the back injury occurred.

Assessing outcomes over 12 weeks, researchers found through imaging, tissue analysis, and mechanical and behavioral tests that the gene therapy restored structural integrity and function to degenerated discs and reduced signs of back pain in the animals.


“This can be used at the same time as surgery to actually boost healing of the disc itself,” said co-senior author Natalia Higuita-Castro, associate professor of biomedical engineering and neurological surgery at Ohio State. “Your own cells are actually doing the work and going back to a healthy state.”

The study was published online recently in the journal Biomaterials.

An estimated 40% of low-back pain cases are attributed to degeneration of the cushiony intervertebral discs that absorb shocks and provide flexibility to the spine, previous research suggests. And while trimming away bulging tissue from a herniated disc during surgery typically reduces pain, it does not repair the disc itself — which continues to degenerate with the passage of time.


This new study builds upon previous work in Higuita-Castro’s lab, which reported a year ago that nanocarriers called extracellular vesicles loaded with anti-inflammatory cargo curbed tissue injury in damaged mouse lungs. The engineered carriers are replicas of the natural extracellular vesicles that circulate in humans’ bloodstream and biological fluids, carrying messages between cells.

To create the vesicles, scientists apply an electrical charge to a donor cell to transiently open holes in its membrane, and deliver externally obtained DNA inside that converts to a specific protein, as well as molecules that prompt the manufacture of even more of a functional protein.

In this study, the cargo consisted of material to produce a “pioneer” transcription factor protein called FOXF1, which is important in the development and growth of tissues.


Compared to controls, the discs in mice receiving gene therapy showed a host of improvements: The tissue plumped back up and became more stable through production of a protein that holds water and other matrix proteins, all helping promote range of motion, load bearing and flexibility in the spine. Behavioral tests showed the therapy decreased symptoms of pain in mice, though these responses differed by sex — males and females showed varying levels of susceptibility to pain based on the types of movement being assessed.

The findings speak to the value of using universal adult donor cells to create these extracellular vesicle therapies, the researchers said, because they don’t carry the risk of generating an immune response. The gene therapy also, ideally, would function as a one-time treatment — a therapeutic gift that keeps on giving.


There are more experiments to come, testing the effects of other transcription factors that contribute to intervertebral disc development. And because this first study used young adult mice, the team also plans to test the therapy’s effects in older animals that model age-related degeneration and, eventually, in clinical trials for larger animals known to develop back problems.


Story Source:

Materials provided by Ohio State University. Original written by Emily Caldwell. Note: Content may be edited for style and length.

Journal Reference:

  1. Shirley N. Tang, Ana I. Salazar-Puerta, Mary K. Heimann, Kyle Kuchynsky, María A. Rincon-Benavides, Mia Kordowski, Gilian Gunsch, Lucy Bodine, Khady Diop, Connor Gantt, Safdar Khan, Anna Bratasz, Olga Kokiko-Cochran, Julie Fitzgerald, Damien M. Laudier, Judith A. Hoyland, Benjamin A. Walter, Natalia Higuita-Castro, Devina Purmessur. Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain. Biomaterials, 2024; 308: 122562 DOI: 10.1016/j.biomaterials.2024.122562

Source: Gene therapy relieves back pain, repairs damaged disc in mice | ScienceDaily

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