Chronic back pain due to disc degeneration is challenging to manage. However, regenerative medicine is progressing. Gene therapy may help promote disc regeneration, but challenges regarding its delivery remain. The new study identified a safer way of delivering gene therapy locally using extracellular vesicles, a method much safer than genetically modified viruses as gene therapy carriers.
Millions of people in the US are living with chronic pain syndromes like back pain. It is a condition that is not just challenging to treat. Relapses are also common in the condition.
Drugs like opioids may help reduce pain sensation, but they are not the cure. Moreover, prolonged opioid use is associated with various health risks. The same is true for other drug therapies. Thus, there is a need to find a better treatment for the back pain.
But why are chronic pain syndromes like the back pain are so challenging to manage? This is due to the complex nature of the problem. These conditions occur for many reasons, like degenerative changes in the spinal disc, mood disorders, and other issues.
Many patients may benefit from regenerative medicine focused on promoting spinal disc regeneration since disc degeneration is the cause of constant pain in many instances. Moreover, such a treatment would be better than surgical interventions that often fail to provide pain relief.
Researchers have been testing many regenerative therapies, like gene therapy, in recent years. However, delivering the gene therapy remains a challenge. For example, genetically modified viruses may help, but such a treatment is associated with certain health risks.
Researchers used nanocarriers to carry modified genes to the target in the new therapy published in Biomaterials. These nanocarriers were modified extracellular vesicles that the human body uses to transport various bioactive compounds or communicate between the cells.
A New Kind of Nanocarriers Can Effectively Carry Modified Genes and Help with Spinal Disc Regeneration
Researchers have demonstrated that engineered extracellular vesicles (EVs) carrying genetic material, specifically the developmental transcription factor FOXF1, can effectively repair degenerative tissue in mouse intervertebral disc (IVD) joints. This minimally invasive approach may be good for managing degenerative back pain (DBP).
This was among the first studies using engineered EVs (eEVs) in a living organism to deliver transcription factors.
Previous research has explored the use of EVs derived from progenitor cells like mesenchymal stem cells (MSCs) for musculoskeletal therapies. However, these progenitor cell-derived EVs often face clinical challenges, as these cells are difficult to harvest, might promote tumor growth, and cause autoimmune diseases. In contrast, EVs are more readily available from sources like fibroblasts and are free from those health risks. Non-viral gene delivery systems like eEVs offer advantages over viral methods, including better safety profiles, reduced immune responses, and flexibility in cargo cargo. This makes eEVs suitable for repeated use, especially in certain chronic painful conditions requiring prolonged treatment.
The researchers had earlier success in reprogramming human IVD cells with transcription factors Brachyury and FOXF1 in vitro using non-viral transfection methods. Given the clinical limitations of these methods for IVD therapies, the current study investigates the in vivo use of eEVs to deliver FOXF1 to degenerate IVDs in a mouse model. The findings reveal that FOXF1-loaded eEVs significantly improved both the structure and function of degenerative discs compared to controls. It helped increase tissue hydration, disc height, and proteoglycan content, which is essential for healthy IVD function. The study also found improvement in spine function, resulting in greater mobility and lesser disability.
The Bottom Line
The research shows the possibility of using eEVs for gene delivery in regenerative medicine. It shows that developmental transcription factors within eEVs can directly reprogram native degenerated IVD cells, thus reducing pain. While further studies are necessary to compare eEVs with other non-viral methods and evaluate their long-term efficacy, this study provides a compelling case for using eEVs as a therapeutic strategy for DBP and possibly other joint disorders. If you are dealing with chronic pain issues, you may visit Padda Institute for expert consultation and personalized treatment.
Source:
Tang, S. N., Salazar-Puerta, A. I., Heimann, M. K., Kuchynsky, K., Rincon-Benavides, M. A., Kordowski, M., Gunsch, G., Bodine, L., Diop, K., Gantt, C., Khan, S., Bratasz, A., Kokiko-Cochran, O., Fitzgerald, J., Laudier, D. M., Hoyland, J. A., Walter, B. A., Higuita-Castro, N., & Purmessur, D. (2024). Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain. Biomaterials, 308, 122562. https://doi.org/10.1016/j.biomaterials.2024.122562
