NEW DELHIi, Aug 7: New research in zebrafish suggests neck and back pain could be a result of changes in gene activity triggering a breakdown of the spine’s natural shock absorbers — the spinal discs.
Findings published in the journal Communications Biology show that the changes in gene activity can lead to a build-up of minerals in the spine — similar to unwanted bone forming in the wrong place — causing it to harden.
Researchers from the universities of Edinburgh and Bristol in the UK said the findings point to potential future drug targets to treat back pain and suggest zebrafish could be a valuable tool for testing them.
One of the main underlying causes is a gradual breakdown of spinal discs — they cushion bones of the spine — known as intervertebral disc degeneration (IVDD).
The researchers said no drugs are available currently to stop or reverse IVDD, despite the condition being common and costly, adding that surgery remains the only long-term option.
“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,” lead researcher Erika Kague, from the University of Edinburgh’s Institute of Genetics and Cancer, said.
“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,” Kague said.
The researchers bred zebrafish lacking a copy of the gene connected to a protein called collagen IX — which helps hold the disc’s structural fibres together. Previous studies have linked the gene to an early-onset of disc problems.
As the fish aged, their spines developed problems strikingly similar to human disc disease — bones of the spine fused together and the tissue between vertebrae became abnormally hardened with mineral deposits.
The team found that the hardening was preceded by a breakdown in a supportive scaffold layer in the developing spine, well before any mineral began to build up.
Looking at which genes were switched on or off in the fish, the researchers uncovered disruptions to how the body handles fat and a growth-control pathway called mTOR, along with changes in phosphate handling and vitamin A signalling — all processes linked to mineral buildup.
A bone-protecting drug already used for osteoporosis — bisphosphonates — was seen to be able to block the mineral buildup. Restricting the fish’s food intake, or using drugs that dampen fat metabolism, also reduced spinal fusions.
The findings point to phosphate handling and fat metabolism as promising targets for future drugs, the researchers said.
“Our findings establish a valuable model for investigating ligament mineralisation and IVDD, while suggesting phosphate and lipid metabolism pathways as therapeutic routes,” the authors wrote. (PTI)
