A National Institutes of Health (NIH) grant awarded to Arkansas Children’s Research Institute (ACRI) will help scientists at Arkansas Children’s and the University of Arkansas for Medical Sciences (UAMS) take a big step toward verifying a genetic target for potential treatments that reduce life-threatening asthma attacks in children.
A team led by Joshua Kennedy, MD, principal investigator, and researchers in California and New Mexico will use the two-year $250,000 grant to confirm whether the specific genetic mutation holds the key to asthma attacks made worse by the common cold.
Kennedy has focused his research since 2013 on severe asthma that occurs when children also have a rhinovirus infection, a virus that causes the common cold. Between 60% to 80% of children who seek emergency treatment for asthma also have a rhinovirus.
The NIH-funded study will attempt to isolate a single nucleotide polymorphism (SNP, also referred to as a genetic “snip”) that might make asthmatics more susceptible to rhinovirus infection in a collaboration between Kennedy; David Broide, MD, at the University of California, San Diego; and Daryl Dinwiddie, PhD, at the University of New Mexico.
“If we can connect this genetic SNP variant to enhanced viral infections, I think that is a huge breakthrough for kids everywhere with asthma,” said Kennedy, an associate professor in the UAMS College of Medicine Department of Pediatrics, Division of Allergy and Immunology who sees patients at Arkansas Children’s. “If we are able to sequence that SNP, and know who has it and who is at higher risk, I think we can come up with treatments that are focused on decreasing the number of asthma exacerbations these kids have and improve their quality of life overall.”
Broide is expert in the specific SNP (ORMDL3 asthma risk variant) and will conduct the genotyping. DNA samples collected from patients at Arkansas Children’s will go to Broide’s lab for SNP analysis. Dinwiddie will assist Kennedy with genomic sequencing of the rhinoviruses found in patients.
The study will look at two groups of patients: those with asthma who have the SNP variant and those with asthma who don’t have it. The study will conduct additional analysis based on the type of rhinovirus. Of the three rhinovirus types, A, B, and C, Kennedy said Type A rhinovirus may cause more severe exacerbations in those with the SNP because the ORMDL3 mutation increases the receptor for this virus on cell surfaces.
Kennedy will also use donated human lungs in his lab to compare responses to rhinovirus infections in lungs with the SNP mutation and those without it. Slices of donated so-called “living lungs” can be preserved and revived to conduct such tests.