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North Carolina Looks to Expand Newborn Screening for Severe Genetic Conditions


NEW YORK (GenomeWeb) – Starting next year, families in North Carolina will have the option of enrolling in an expanded newborn screening program that simultaneously seeks to diagnose severe genetic conditions and serve as a research study on these conditions and potential treatments.

Dubbed Early Check, the program will initially provide expanded testing for fragile X syndrome and spinal muscular atrophy (SMA), neither of which are included in states' traditional newborn screening tests. As the study progress, researchers will have the option to gradually add other disorders to the Early Check testing panel.

RTI International is spearheading the study in partnership with the North Carolina State Laboratory of Public Health, the University of North Carolina, Duke University, and Wake Forest Baptist Medical Center. The National Institutes of Health through its National Center for Advancing Translational Sciences awarded collaborators $1 million per year over the next five years to launch the program.

Currently, the researchers are in the process of determining screening technologies and follow-up protocols, and plan to launch the study in select locations in April 2018, rolling it out to the entire state after a six-month trial period.

The goal of the study is to facilitate research on early intervention for serious genetic disorders, Don Bailey, the lead investigator of the study, said in an interview. "Researchers are caught in a Catch-22 situation," he said. "They can't mandate newborn screening for these conditions because there is not enough evidence, but they can't get the evidence without a major screening program." Early Check aims to fill that gap. A longer-term goal, Bailey said, will be to impact policy decisions around what disorders should be included in the state newborn screening test.

The program will be optional, although the researchers hope to recruit as many newborns in North Carolina as possible, Bailey said. He said the team is pursuing a two-pronged approach for enrolling parents. There will be an awareness campaign targeting expecting parents with information made available at family medicine offices and at the offices of Ob/Gyns. Those physicians will not be able to recruit patients, however, since that would require that they be part of the institutional review board protocol. But, individuals will be able to sign up on their own online. In addition, after the baby is born and the standard newborn screening is done, the North Carolina State Laboratory of Public Health will invite the parents to participate.

The researchers are still figuring out the exact testing methodology and whether tests will be laboratory developed or commercial. Bailey said that will depend in part on what level of US Food and Drug Administration approval will be required. Most likely though, he said, the team will use a real-time PCR assay for SMA testing. For fragile X testing, they will likely use PCR and capillary electrophoresis.

If a family tests positive for one of the disorders, the research team at RTI, UNC, Duke, and Wake Forest will work with families' primary care physicians to make sure they are aware of the available treatment and clinical trial options. Although the study is not linked to a specific clinical trial, Bailey said, "we'll help make sure the parents know about the various trials that they might be eligible for."

Fragile X and SMA were chosen as the first disorders to test the benefits of early diagnosis because they are both common enough in the population that a significant number of affected children will be identified. In addition, for both disorders "there is a real need for studies that look at the benefit of early intervention," particularly for presymptomatic testing of treatment, Bailey said.

For instance, historically there have not been any treatment options for SMA, Bailey said, but over the last four to five years, some companies have made promising advances in new medications and gene therapy approaches.

SMA is estimated to occur in one in 10,000 individuals, while Fragile X occurs in one in approximately 5,000, Bailey said. There are an estimated 120,000 births per year in North Carolina and Bailey said that if the researchers are able to eventually reach a 65 percent participation rate, he would consider that a success. That would result in around 70,000 babies being screened, which should identify seven to eight with SMA and 14 with fragile X.

A second aim of the study will be to follow up with newborns and their families who are diagnosed with either fragile X or SMA. After newborns receive a diagnosis, the parents will go through another consent process to enter into a registry to enable the researchers to follow up with them and see how the diagnosis and potential early treatments made a difference in their outcomes. While the NIH grant is for five years, Bailey said that one goal would be to set up a long-term, sustainable system that would last beyond the grant. That would likely require a public/private partnership, he said.

"We want to know at the disease level if we can create a model that shows that earlier identification has demonstrable benefits," he said. "If so, that could help accelerate the approval of those conditions for regular newborn screening." Alternatively, he said, the study might find that testing for those disorders at birth doesn't make a difference in outcome. Either way, he said, "we want to make a policy decision that is evidence based."

Population-level testing of SMA and fragile X might also refine the incidence of the diseases, he said. Disease incidence is estimated primarily based on symptomatic babies who are seen at clinics. "But, there may be individuals who have milder symptoms and aren't diagnosed or who are misdiagnosed," he said.

The Early Check study is more limited in scope than the suite of NIH-funded newborn screening programs that are evaluating the potential of genomic sequencing at birth, but is more focused on studying the impact of early diagnosis and helping to advance translational research for the specific disorders of Fragile X and SMA. Bailey said that his team is also involved in a UNC study dubbed NC Nexus that aims to sequence the exomes of 400 newborns. The RTI group is developing a decision aid to help parents decide if they want the sequencing and if so, what results they want returned.

Bailey noted that the Early Check study is "more immediately relevant because we're diagnosing specific conditions," looking at the impact on outcomes, and potentially affecting newborn screening policy.