UF scientists unmask gene activity in scoliosis

GAINESVILLE, Fla. — A curvature of the spine known as adolescent idiopathic scoliosis is the most common type of pediatric spinal deformity, affecting up to 3% of children worldwide.

The disease has long retained its secrets.

A team of University of Florida Health researchers, however, has conducted one of the first direct comparisons of gene activity in spinal tissue from adolescents with the condition, also called AIS, and unaffected individuals, unraveling key biological mechanisms in a study published in June.

“This study gives us one of the clearest pictures yet of what is happening at the molecular level in scoliosis patients,” said the study’s senior author, Nadja Makki, Ph.D., an assistant professor in the UF College of Medicine’s Department of Physiology and Aging. “Now, we basically have a list of genes that we can sort, and we can see exactly which of those are behaving differently in spinal tissues affected by scoliosis.”

The study was published in Human Genetics and Genomics Advances.

Obtaining tissue from young adults without the disease has always been the stumbling block to conducting such a comparison. UF Health researchers, however, created a tissue biobank that enabled the analysis. In addition to obtaining tissue from AIS patients, they collected waste tissue from young adults undergoing spinal surgery unrelated to AIS after receiving consent.

The research team analyzed gene activity in two types of tissue involved in scoliosis development. The first was cartilage in the spine, followed by the adjacent muscle supporting it.

Their findings showed that each tissue in AIS patients exhibited a distinct pattern of abnormal gene activity, suggesting scoliosis might may arise from multiple biological processes occurring at once.

Researchers also found important differences in genes involved in cartilage development, particularly those that help specialized cartilage cells form properly. In muscle tissue, they discovered abnormal activity in genes that help muscles contract and maintain strength.

Future studies can build on these findings to better understand the biological mechanisms driving AIS, the researchers said.

The research opens the possibility of identifying children at risk before spinal curvature progresses enough to require highly invasive and costly surgery.

“If we could identify these patients prior to them developing that large curvature, then we could put that child in a brace, or we could do scoliosis-specific exercises,” said study co-author Jessica McQuerry, M.D., a pediatric orthopaedic surgeon and an assistant professor in the UF College of Medicine’s Department of Orthopaedic Surgery and Sports Medicine. “We have preventive therapies that do work, but we don’t know who to use them on.”

Current scoliosis treatment largely begins only after spinal curvature has already developed, leaving physicians focused on slowing progression rather than preventing the condition altogether.

“Adolescent idiopathic scoliosis is a condition that we’re very reactive to,” said study co-author Stephanie Ihnow, M.D., an associate professor and surgeon who is also in orthopaedics. “And what we’re trying to do is to be more proactive instead of reactive.”

AIS usually occurs during the child’s most rapid growth period, with spinal curvature for some progressing even into adulthood, with curves of greater than 60 degrees in some individuals, according to the Scoliosis Research Society.

The disease occurs in both boys and girls, but progressive cases are far more common in girls.

UF Health Pediatric Orthopaedics is an Alliance with Shriners Children's at UF Health Orthopaedics and Sports Medicine.