Changes in gene activity may reveal new drug targets for chronic back pain by showing how spinal discs break down, zebrafish research suggests.
The changes can cause minerals to build up in the spine, similar to unwanted bone forming in the wrong place, making it harden.
Dr Erika Kague, study lead from 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.”
Back pain affects most people at some point in their lives. A major underlying cause is the gradual breakdown of spinal discs, which cushion the bones of the spine.
This condition is known as intervertebral disc degeneration, or IVDD.
Despite how common and costly IVDD is, there are currently no medicines that can stop or reverse it. Surgery remains the only long-term treatment option.
Genetics are known to play a role in IVDD.
A gene linked to collagen IX, a protein that helps hold the structural fibres of spinal discs together, has repeatedly been associated with disc problems that begin early in life.
Scientists from the universities of Edinburgh and Bristol studied zebrafish bred without a working copy of the gene to examine how genetic faults could cause disc disease.
As the fish aged, their spines developed problems similar to those seen in people with the condition.
The spinal bones fused, while tissue between the vertebrae became abnormally hardened by mineral deposits.
The researchers found that this hardening followed the breakdown of a supportive scaffold layer in the developing spine, well before minerals began to accumulate.
The team then examined which genes were switched on or off in the fish.
It found changes in fat metabolism and mTOR, a biological pathway that controls cell growth and how cells respond to nutrients.
The researchers also identified disruptions in phosphate handling and vitamin A signalling, which are linked to mineral build-up.
The team tested several ways of reducing the damage.
A bisphosphonate, a bone-protecting medicine already used to treat osteoporosis, prevented the mineral deposits from forming.
Restricting the fish’s food intake and using medicines that reduced fat metabolism also lowered the number of spinal fusions.
The findings point to phosphate handling and fat metabolism as possible targets for future medicines, the researchers said.
The research was supported by Arthritis UK and the Biotechnology and Biological Sciences Research Council.
Dr Caroline Aylott, head of research delivery at Arthritis UK, said: “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.
“We are proud to fund research that is unlocking the science behind the processes leading to spinal disc degeneration.
“Back pain is one of the UK’s most common conditions that has blighted millions over generations.
“Dr Erika Kague and her team at the University of Edinburgh have uncovered important genetic evidence that could pave the way for new treatments, bringing us one step closer to a future where fewer people have to live with the daily pain and challenges that back pain can bring.”
