Treating back pain caused by issues with spinal discs could potentially be resolved through gene therapy, as indicated by a recent study. This approach involves using naturally derived nanocarriers to administer the therapy, which has been shown to repair damaged discs in the spine and alleviate pain symptoms in mice. Scientists developed these nanocarriers by using fibroblasts, a type of connective tissue cell found in mice, as a model for skin cells. They then loaded these nanocarriers with genetic material for A crucial protein for tissue development has been discovered by a team. They injected a solution containing carriers into damaged discs in mice simultaneously with the back injury. Over a 12-week period, the researchers assessed the outcomes and discovered that the gene therapy restored structural integrity and function to degenerated discs. Additionally, it reduced signs of back pain in the animals through imaging, tissue analysis, and mechanical and behavioral tests. Co-senior author Devina Purmessur Walter, associate professor of biomedical engineering at The Ohio State University, stated, “We have this unique strategy that’s able to both regenerate tissue and inhibit some symptoms of pain.”rsity.
Despite the need for further research, the results indicate that gene therapy may provide a lasting and effective alternative to opioids for treating severe back pain.
Co-senior author Natalia Higuita-Castro, an associate professor of biomedical engineering and neurological surgery at Ohio State, explained, “This can be used alongside surgery to enhance the healing process of the disc itself. Your body’s own cells are responsible for the healing, ultimately restoring it to a healthy state.”
The findings of the study were recently published online in the journal Biomaterials.
An estimated 40% of individuals suffer from back pain, and it is one of the most common reasons for disability worldwide.Low-back pain cases are often caused by the deterioration of the intervertebral discs, which are responsible for absorbing shocks and allowing the spine to move. Research has shown that while removing the bulging tissue from a herniated disc can reduce pain, it does not fix the disc itself. This means that the disc will continue to deteriorate over time.
Walter Purmessur explained, “When you remove part of the disc, it loses its shape and function, similar to a deflating tire. This ongoing deterioration can also affect the neighboring discs because the necessary pressure for spinal function is lost. Currently, clinicians do not have a good solution for this issue.”The study mentioned in the article builds on previous research conducted by Higuita-Castro’s lab, which demonstrated that nanocarriers known as extracellular vesicles loaded with anti-inflammatory cargo helped to reduce tissue damage in injured mouse lungs. These engineered carriers are designed to mimic the natural extracellular vesicles found in the human bloodstream and biological fluids, which play a role in carrying messages between cells.
In order to create these vesicles, scientists use an electrical charge to temporarily open holes in a donor cell’s membrane and then introduce externally obtained DNA that can be converted into a specific protein, as well as molecules that The study aimed to stimulate the production of a crucial protein.
The material transported in this study was used to create a fundamental transcription factor protein known as FOXF1, which plays a critical role in tissue development and growth.
According to Purmessur Walter, “Our approach involves mimicking development: FOXF1 is active during development and in healthy tissue, but its levels decrease as we age. Essentially, we are attempting to deceive the cells and restore them to their developmental state when they are growing and at their healthiest.”
Experiments involved treating mice with injured discs using FOXF1 nanocarriers and comparing the results to untreated mice.
Injured mice were given saline or mock nanocarriers, while uninjured mice served as the control group. The mice that received gene therapy showed significant improvements in their spinal discs compared to the control group. The tissue regained its volume and stability due to the production of a protein that helps hold water and other matrix proteins, ultimately improving the range of motion, load-bearing capacity, and flexibility in the spine. The therapy also reduced pain symptoms in the mice, with varying responses based on sex – males and females showed different levels of pain susceptibility depending on the type of movement being assessed.The researchers emphasized the importance of using universal adult donor cells for creating these extracellular vesicle therapies, as they do not pose the risk of triggering an immune response. Additionally, the gene therapy is designed to function as a one-time treatment, providing long-lasting therapeutic benefits.
“The concept of cell reprogramming involves the expression of a specific transcription factor, which then prompts the cell to transition into a healthier state and remain committed to that state, without the need for repeated doses,” explained Higuita-Castro.
More experiments are planned to test the effects of other transcription factors that contribute to intervertebral disc development. The initial study used young adult mice, but the team intends to also 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.
Higuita-Castro, director of advanced therapeutics and engineering in the College of Medicine Davis Heart and Lung Research Institute and a core faculty member of Ohio State’s Gene Therapy Institute, and Purmessur Walter, an investigator in Ohio State’s
The Spine Research Institute and the director of the Spinal Therapeutics Laboratory in the College of Engineering are both co-principal investigators on National Institutes of Health grants that fund this research. Other co-authors of the study include Shirley Tang, Ana Salazar-Puerta, Mary Heimann, Kyle Kuchynsky, MarÃa Rincon-Benavides, Mia Kordowski, Gilian Gunsch, Lucy Bodine, Khady Diop, Connor Gantt, Safdar Khan, Anna Bratasz, Olga Kokiko-Cochran, Julie Fitzgerald, and Benjamin Walter, all from Ohio State University. Damien Laudier is from the Icahn School of Medicine at Mount Sinai, and Judith Hoyland is from the University of Manchester. Ohio State University is also involved in the research.A patent application has been submitted for a nonviral gene therapy for minimally invasive treatment of painful musculoskeletal disorders.
