ScoliosisAbnormal lateral curvature of the spine.
What is Scoliosis
Adolescent Idiopathic Scoliosis (“AIS”) is a medical condition defined as a spinal curvature of more than 10 degrees to the right or left as the examiner faces the patient. Deformity may also exist to the front or back. Currently, best practice is to observe a child with an early stage curvature of the spine. The child is then monitored and x-rayed every quarter. Medical monitoring and x-rays are expensive, repetitive x-ray exposures carry a risk and these practices create a potentially unnecessary stress on the child and family. The children are often, unnecessarily placed in a brace. An estimated 6 million people have scoliosis in one form or another. The primary age range for onset of idiopathic scoliosis is 10-15, occurring equally in both genders but females are eight times more likely to progress to curve magnitude that requires intervention. Idiopathic or degenerative scoliosis is the cause of 600,000 physicians visits annually. An estimated 30,000 children put in braces and 38,000 patients undergo spinal fusion surgeries. Scoliosis is also an inherited disease. There are over 100,000 new cases of AIS diagnosed in the United States annually.
Presently, AIS is diagnosed and then treated almost entirely by a time lapse series of x-rays which form the basis for measuring the patient’s curve magnitude (the only caveat being that brace treatment is thought to be effective only in patients who are still growing). A typical case would be a young patient whose parents have noticed excessive spine curvature or the patient complaining of back pain. The physician takes a series of X-rays and measurements and if AIS is diagnosed, begins a treatment plan consisting of observation (via X-ray) of curves less than 30°, brace curves in the 30°–40° range and perform surgery if curves exceed 40°. Notice that each decision point rests on a 10° increment—including between observation and major spinal surgery. In fact, 10° is also the commonly discussed margin of error for measuring scoliotic curves. Then there is the added issue of rapidly growing adolescents. A 13-year-old child can suddenly hit a growth phase and go from 16°–26° literally overnight.
PRx’ Genetic Scoliosis Test will dramatically change the way that scoliosis is diagnosed and treated in the United States. After years of development, testing DNA samples from more than 9,000 patients, tracking billions of genotypes and making trillions of calculations, the specific, genetic markers for scoliosis were found. It is significant because it will enable physicians to use a simple test to accurately identify before taking dozens of X-rays and prescribing extensive bracing—which patients will progress to a severe stage. Not only will this save millions of dollars, but it also will change the treatment paradigm to one with earlier and presumably more successful intervention.
Sensitivity and specificity were confirmed in two clinical trials, with each trial including over 400 scoliosis patients. The Negative Predictive Value in the intended use population is 93%–98% (89–100), as confirmed by the clinical trials. These landmark studies have provided researchers with greater insights into the genetic markers associated with spinal curve progression. The AIS Prognostic Test, which can determine whether a child has a mild or more severe likelihood of curve progression, at the very first presentation of symptoms, will provide comfort to thousands of children and their families every year. The use of this DNA-based testing to determine the likelihood of disease progression will initiate a new era of improvements in spine health in children. From a clinical standpoint, this test delivers the promise of personalized medicine to spine surgeons who will now have the ability to accurately determine the likely disease progression for an individual AIS patient, and they can make evidence-based recommendations for patient-specific treatment options.”
The test comprises a saliva-based 53 SNP marker panel that predicts the risk of curve progression to a severe curve by skeletal maturity. Indication is for Caucasians between the ages of 9-13 diagnosed with mild AIS (10-25 degree Cobb angle). Clinical studies are in progress with the objective to modify test for other ethnicities. Approx. 9,500 individuals have been tested during R&D, subsequently two validation trials with >800 AIS patients & 1,000 controls. The specificity of Scoliosis Test is 99% (99-100%). Specificity: true negative rate “I know my patient doesn’t have the disease. The sensitivity of scoliosis test is 85% (84-85%). Sensitivity: true positive rate “I know my patient has the disease. What is the chance that the test will show that my patient has it?”. The test is highly actionable; it has clinical validity and utility.
The practical outcome of the AIS molecular diagnostic test is that the 80% of the children being tested will receive a reliable genetic diagnosis/prognosis in an early stage that their disease will not develop to a severity that will benefit from treatment. This means that the children will not need to be braced, not need to receive quarterly x-rays of their spines, and more importantly, stop stressing about the future of their spines and spending time and money on treatments. They get to go back to a normal life without the fear of treatments, surgeries or a lifelong debilitating condition.