Gene therapy improved intervertebral disc health and relieved pain in mice
American scientists have developed a gene therapy that uses engineered extracellular vesicles to deliver a transcription factor. After such delivery of the FOXF1 transcription factor into degenerative intervertebral discs in diseased mice, the intensity of pain syndrome decreased and the discs themselves began to perform mechanical functions better. The design and study report is published in the journal Biomaterials.
Painful musculoskeletal disorders (e.g. chronic low back pain) are considered the leading causes of disability worldwide; their prevalence and impact on society continues to increase due to an aging population. Degeneration of the intervertebral disc is a major cause of low back pain, accounting for approximately 40 per cent of pain cases. This process involves mechanical disruption of the disc, loss of essential components of the extracellular matrix (particularly proteoglycans), increased catabolism, inflammation and neurovascular invasion. All of this leads to loss of tissue function and increased pain.
Current treatments for intervertebral disc degeneration are limited to temporary pain relief or invasive expensive surgical procedures that do not address the underlying pathology or disease mechanisms. Therefore, there is a need for minimally invasive therapeutic strategies to restore tissue structure and function that can provide long-term pain relief.
A team of scientists led by Devina Purmessur at Ohio State University has engineered extracellular vesicles capable of carrying the transcription factor FOXF1, which is involved in the expression of the foxf1 gene responsible for the development of lung and gastrointestinal mesenchyme. Using puncture, these vesicles were delivered into the damaged intervertebral lumbar discs of mice, with which the preliminary efficacy of this therapy was evaluated. These vesicles were obtained after transfection of primary mouse embryonic fibroblasts with an expression plasmid encoding FOXF1.
After puncture of the preparation into the injured intervertebral disc, model mice in tests began to exhibit behaviours characteristic of pain reduction. Thus, male mice that received vesicles with FOXF1 showed reduced hypersensitivity to cold after 12 weeks compared to the control group, indicating a reduction in pain behaviour. In addition, the experimental mice showed significant restoration of intervertebral disc structure and function. Specifically, the scientists found a significant increase in disc height and tissue hydration, as well as an increase in proteoglycan concentration. Together, these restored the mechanical function of the intervertebral discs.
While the scientists recognise that the introduction of treatments based on engineered extracellular vesicles into clinical practice has been hampered by low efficacy, heterogeneity and limited scalability, they also believe that this study has promising results. For example, the minimally invasive procedure of delivering vesicles into intervertebral discs has the potential to relieve pain syndrome that limits the performance of many people.