An existing osteoporosis drug has been shown to block abnormal mineral buildup in the spines of genetically modified zebrafish, according to new research from the Universities of Edinburgh and Bristol. The findings raise the prospect of future drug treatments for intervertebral disc degeneration, a cause of back pain for which no medication can currently stop or reverse the degenerative process.
Intervertebral disc degeneration occurs when the discs cushioning the vertebrae lose their ability to absorb pressure. Despite its widespread impact, surgery remains the only established long-term intervention for certain severe cases; no medications are currently available to stop or reverse the degenerative process.
The study, published in Communications Biology, investigated a gene associated with collagen IX, a protein that helps maintain the structural integrity of spinal discs. Researchers bred zebrafish without a functioning copy of the gene to observe how its absence affected the spine.
As the fish aged, abnormal mineral deposits accumulated in the tissues between their vertebrae, and neighbouring vertebrae began to fuse together. The scientists discovered that the damage began before the mineral deposits appeared, with an underlying structural layer breaking down first.
One of the most promising results came when the team tested a medication from the bisphosphonate class, already used for osteoporosis. The medication successfully blocked the abnormal mineral buildup in the zebrafish.
The researchers also identified changes in fat metabolism and in a cellular signalling system called mTOR. Limiting how much the zebrafish ate, and medications that suppressed fat metabolism, each led to fewer spinal fusions.
Dr Erika Kague, who led the research at the University of Edinburgh's Institute of Genetics and Cancer, said: "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."
Dr Caroline Aylott, Head of Research Delivery at Arthritis UK, said the research brought “fresh hope” that potential new therapeutic approaches were on the horizon for the 9.5 million people across the UK living with back pain. Dr Jef Grainger of BBSRC, which supported the work, added that the study showed how publicly funded discovery bioscience can generate the knowledge needed to address major health challenges.
The experiments were conducted in zebrafish, and the researchers caution that more research is needed to determine whether the same mechanisms operate in humans and whether targeting them is safe and effective.
Analysis
Why This Matters
- Explores a new biological mechanism behind disc degeneration, a massively common health problem.
- Repurposing an existing approved drug could drastically cut the time and cost of developing a treatment.
- Opens the door to the first drug therapies for a condition that currently only has surgery as its long-term solution.
Background
Intervertebral disc degeneration is a condition where the discs cushioning the vertebrae break down. Despite affecting millions, no medications are available that can stop the process. Surgery is the only established long-term treatment. The study investigated genetic variations affecting collagen IX, a protein that maintains the structural integrity of spinal discs, and their link to early disc problems.
What to Watch
- Whether clinical trials in humans are initiated to test bisphosphonates for spinal disc degeneration.
- If the identified metabolic pathways lead to separate drug development programs.
- Results from follow-up studies seeking to confirm the mechanisms in human tissue or animal models closer to humans.
Checked
12 claims in this story checked against 1 source: 12 supported.
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- SupportedAn existing osteoporosis drug blocked abnormal mineral buildup in zebrafish spines.Latest Science News -- ScienceDaily: “A medication belonging to a class of drugs called bisphosphonates successfully blocked the abnormal mineral buildup in the zebrafish.”
- SupportedResearchers identified genetic and metabolic changes linked to disc degeneration.Latest Science News -- ScienceDaily: “Researchers also identified changes in gene activity and metabolism that appear to contribute to this damage”
- SupportedThe findings point to potential future treatments for chronic back pain.Latest Science News -- ScienceDaily: “they suggest that medications already used for other conditions could offer new ways to slow spinal degeneration.”
- SupportedThe research was from the Universities of Edinburgh and Bristol.Latest Science News -- ScienceDaily: “scientists at the Universities of Edinburgh and Bristol turned to zebrafish.”
- SupportedNo medications are currently available to stop or reverse the degenerative process.Latest Science News -- ScienceDaily: “no medications are currently available that can stop or reverse the degenerative process.”
- SupportedDr Erika Kague said: “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.”Latest Science News -- ScienceDaily: “"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."”
- SupportedA bisphosphonate medication successfully blocked abnormal mineral buildup in the zebrafish.Latest Science News -- ScienceDaily: “A medication belonging to a class of drugs called bisphosphonates successfully blocked the abnormal mineral buildup in the zebrafish.”
- SupportedThe damage began before mineral deposits appeared, with an underlying structural layer breaking down first.Latest Science News -- ScienceDaily: “the scientists discovered that the damage began well before the mineral deposits appeared. An underlying layer that provides structural support during spinal development started to break down first”
- SupportedLimiting how much the zebrafish ate led to fewer spinal fusions.Latest Science News -- ScienceDaily: “Limiting how much food the zebrafish consumed led to fewer spinal fusions”
- SupportedDr Caroline Aylott said the research brought “fresh hope” for potential new approaches for the 9.5 million people across the UK living with back pain.Latest Science News -- ScienceDaily: ““For the 9.5 million people across the UK living with back pain this research brings fresh hope that potential new therapeutic approaches are on the horizon.””
- SupportedDr Jef Grainger of BBSRC said the study showed how publicly funded discovery bioscience can generate knowledge needed to address major health challenges.Latest Science News -- ScienceDaily: “Dr. Jef Grainger, Executive Director for Bioscience Advancing Knowledge at BBSRC, said: "This research shows how publicly funded discovery bioscience can generate the knowledge needed to address major health challenges.”
- SupportedMore research is needed to determine whether the same mechanisms operate in humans and whether targeting them is safe and effective.Latest Science News -- ScienceDaily: “More research will be needed to determine whether the same biological mechanisms operate in people and whether targeting them can safely prevent or slow spinal disc degeneration.”