Personalized medicine, providing treatments tailored to individual factors down to the molecular level, is a promising approach for a highly variable disease like cystic fibrosis (CF). The approach is particularly important for children with CF, a group at particular risk of health complications that last for decades.
CF, an inherited disease, is well-positioned to take advantage of personalized medicine because it is a monogenic disorder — i.e., the result of mutation(s) in a specific gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene — and has a well-characterized pathophysiology with clear therapeutic targets. CF diagnosis also often comes through genetic testing, leading to a high rate of mutation identification in this population.
DNA screening tests detect most CF cases at birth, but the disease has a wide spectrum of severity, which available early screening tests cannot distinguish or predict. There is no marker to determine which patients will barely show symptoms and which are at risk for persistent lung infections.
“Now we’re flying blind,” Hara Levy, MD, a physician at Ann & Robert H. Lurie Children’s Hospital of Chicago, said in a news release. Dr. Levy and her lab team are working to map the molecular underpinnings of the CF clinical experience.
Dr. Levy is using samples from CF patients to examine how specific gene sets are expressed over time in relation to disease severity, patients’ clinical course, response to therapies, and variables including family history, age, and specific CFTR mutations. Her laboratory is the only one in the CF field currently conducting this kind of front-line research.
“Our ultimate goal is to be able to tailor medical care to individual patients according to their molecular profile differences,” said Dr. Levy, director of Pulmonary Research at Stanley Manne Children’s Research Institute and an associate professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. She expects that tailored care could begin with the disease’s diagnosis.
As an example, she said that differences in molecular patterns may signal if a patient’s lung infection is bacterial or viral, which would determine the need for treatment with antibiotics. Or, clinicians may be able to understand if a child with CF is developing diabetes even before the appearance of symptoms.
“We are hoping to use patient-specific molecular signatures to predict how the disease manifests and responds to treatment, which would allow us to intervene earlier and more effectively,” said Dr. Levy.
The early molecular warning signs could determine treatments, and disease outcomes. “At this stage, our genomic studies have identified predictive biomarkers that may be targets for treatment of lung severity in cystic fibrosis,” she said.
Dr. Levy’s study is co-funded by the National Institutes of Health’s New Innovator Award, the National Heart, Blood and Lung Institute, and the Stanley Manne Children’s Research Institute.