Texas Scottish Rite Hospital: DNA ‘biobank’ leading to new research breakthroughs

Research Texas

Texas Scottish Rite Hospital

2222 Welborn St.

Dallas 75219

214-559-5000

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www.tsrhc.org

Founded in 1921 by orthopedic surgeon W. B. Carrell and a group of local Masons, Texas Scottish Rite Hospital for Children is a leading pediatric center for the treatment of orthopedic conditions and sports injuries, as well as certain related neurological disorders and learning disorders, such as dyslexia. Patients receive treatment regardless of the family’s ability to pay.

—– More than 20 years ago, orthopedic surgeons treating children with various bone growth disorders at Texas Scottish Rite Hospital for Children in Dallas began collecting DNA from tissue and blood samples for research into the underlying mechanisms that cause scoliosis and the other complex diseases they were treating.

There were no animal models or cell cultures that could be used in basic research to learn what drives the disease processes that cause spinal deformities, clubfeet, hip disorders, abnormal growth in arms, legs, fingers and feet and other disorders.

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Today, the Scottish Rite Hospital “biobank” contains cell samples and other information from more than 2,000 families, including three generations of data from some families.

“Our freezer is our Fort Knox, filled with tiny bits of gold that our families have shared with us,” said Dr. Carol Wise, whose research team has now identified a number of genetic risk factors for scoliosis, the most common spinal deformity in children.

One study provides the most definitive link yet between the neurological system and the spinal system in the development of scoliosis.

“For many decades scoliosis has been addressed as a disease of the bones and muscles. This research suggests that the nervous system may be important in the disease and is pointing us toward genes that tell the nerves how to grow,” Wise said.

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“We are at a very exciting time with several big breakthroughs in understanding some of these bone diseases in children at a very basic molecular level,” she said. “We are discovering what makes bones grow, why they break and what can make them heal better.”

And, on a more general level, they have learned that while scoliosis seems to affect an equal number of boys and girls in school screenings, girls outnumber boys 5 to 1 in treatment settings and 10 to 1 in cases severe enough to require surgery.

“Last year a study found that one of the genes associated with scoliosis is female specific. It was the first discovery of a female-specific factor in adolescent idiopathic scoliosis. Now we are looking at hormonally controlled mechanisms for the disparity.,” she said.

Wise has been chief genetic researcher at Scottish Rite for 20 years and is director of molecular genetics. She also has just been elevated to director of basic research.

“What we do here is patient-focused,” she said. “To be in the room together with not only other researchers but also clinicians and patients is invaluable. What we do in the hospital caring for patients is very important to what we see in the patients we are studying in our research. To have that close physical connection – we are only two floors above the clinic – is so important.”

While some researchers are looking for physicians to collaborate with, researchers and physicians at TSRHC “are working right here together with patients, Wise noted.

Research at Scottish Rite is focused on new treatments for musculoskeletal conditions included in what are identified as Centers for Excellence: spine research, limb lengthening and reconstruction, the hand center, clubfoot research, hip disorders and sports medicine. Research is directed toward underlying causes, early detection and both medical and surgical ways to halt progression of disease.

Researchers also are looking carefully at the possible negative side effects of certain procedures and treatments to better determine which patients truly benefit from the most aggressive treatments, over the long term.

They are still finding better ways to surgically treat idiopathic adolescent scoliosis – ways to make surgery easier, more precise and more effective, but they also are looking for the underlying causes and possible prevention and for the complex combinations of genes that put some children at risk for the disease.

Research, clinical care and medical education, are the three major components of Scottish Rite’s mission: to discover new and innovative ways to best care for children affected with orthopedic and certain related neurological conditions.

“We have a very comprehensive research program from clinical to basic science,” said Dr. Harry Kim, director of the Sarah M. and Charles E. Seay Center for Musculoskeletal Research at the hospital. “It actually got started in the late ‘80s, but has really taken off in the last 10 years or so.”

Scottish Rite specializes in children’s orthopedic conditions, and everyone who works there contributes to research, which also helps the hospital collect large clinical outcomes data to assure that things like infection rates, unnecessary treatment and delays in mobility are kept at a minimum, Kim said.

His own research focuses on Perthes disease, a degenerative hip disorder caused by a lack of blood flow to the femur head. With minimally invasive surgery to create multiple channels in the bone, orthopedic surgeons are now able to restore blood flow when aggressive treatment is required.

The hospital gets more than 40 applications from all over the world for its five fellowship positions each year, and also hosts four orthopedic residents. They are all required to do some research work, Kim said.

With expert researchers, biomedical engineers, physicians, research coordinators, nurses, staff and patients all under one roof, Scottish Rite has a record of multidisciplinary collaboration that has generated more than 20 patents and developed systems for spine surgery and limb lengthening that are used all over the world.

“The big, big advantage is that the patient doesn’t get lost in all of this. All of us focus on the same thing – how best to treat our patients,” said Dr. Tony Herring, chief of staff emeritus, who really got the clinical research ball rolling at Scottish Rite about 25 years ago.

Basic scientific research into the cause, affects and risk factors for bone diseases in children took off with the in-house biological data bank on children treated at Scottish Rite Hospital.

“We are expanding basic research here and adding a Center for Bone Biology and Translational Research,” Wise said. “Scottish Rite is leading the way, but to our knowledge there is no population that is spared from adolescent onset idiopathic scoliosis (IS).”

Through the International Consortium for Scoliosis Genetics, she is working in collaboration with researchers from Canada, France, New Zealand, Japan, China – all over the world – on research focused on the genetic risk factors for scoliosis.