A new study using zebrafish has uncovered a surprising potential treatment for spinal disc degeneration, revealing that a drug already prescribed for osteoporosis can block the mineral buildup that hardens spinal tissue.
Researchers discovered that changes in gene activity can lead to neck and back pain by damaging the spine's natural shock absorbers, the discs. In the study, altered gene activity in zebrafish caused minerals to accumulate in the spine, mimicking bone formation in the wrong places and making spinal tissue unusually rigid. These findings pinpoint biological processes that could be targeted for future back pain treatments and suggest zebrafish could be a valuable model for testing new therapies.
The condition, known as intervertebral disc degeneration (IVDD), is a common cause of back pain, but currently, no medications can halt or reverse its progression, leaving surgery as the only long-term solution. While inherited factors are known to play a role, previous research has linked early disc problems to a gene associated with collagen IX, a protein crucial for the structural fibers within spinal discs.
To understand how defects in this gene contribute to disc disease, scientists from the Universities of Edinburgh and Bristol studied zebrafish lacking a functional copy of it. As these zebrafish aged, they developed spinal abnormalities strikingly similar to those seen in human disc disease, including fused vertebrae and hardened disc tissue due to mineral deposits. The mineralization was found to occur only after the initial deterioration of the supportive scaffold layer within the developing spine.
Further analysis of gene activity patterns in the fish pointed to issues with fat processing, the mTOR pathway (which regulates growth), phosphate control, and vitamin A signaling – all processes linked to abnormal mineral accumulation. Excitingly, the researchers found that a bisphosphonate, a type of osteoporosis medication, effectively prevented mineral buildup. Spinal fusion was also reduced when the fish were fed less or treated with drugs that suppressed fat metabolism, highlighting phosphate regulation and fat metabolism as key areas for future drug development.
Dr. Erika Kague, the study's lead from the University of Edinburgh, expressed enthusiasm about the findings, stating, "For decades, surgery has been the only real answer for disc disease. By understanding the biology that drives the spine to harden, our zebrafish studies point to several ways of slowing it down, including a drug already used safely in patients. There's more work to do, but for a condition that's affected people for generations without a treatment in sight, this is super exciting."
