Study authors pinpointed a single gene that was consistently different between the good and bad responder groups, a finding that hinted as to why the non-responsive group wasn't affected by the corticosteroid treatment. That gene was VNN-1, whose pathway is characteristic of additional inflammatory diseases besides asthma, including inflammatory bowel disease and system lupus erythematosus.
To check their results, researchers conducted the study in mice with asthma, and knocked out their VNN-1 before administering the steroid treatment. Sure enough, the mice whose VNN-1 pathway was knocked out, disabling methylation, did not respond to the medication.
"Because of this mouse data, we found [the VNN-1 pathway] is not just a marker but has a causative role," Hershey said.
Drugs already approved by the Food and Drug Administration (FDA) target the VNN-1 pathway, including one for kidney disease, so researchers say repurposing them may provide a therapy for hard-to-treat childhood asthma patients in the future. Hershey's team is now analyzing how those drugs affect mice with asthma.
The VNN-1 pathway also is involved in the synthesis of vitamin B. Humans aren't known to be vitamin B deficient, as diets typically are rich in the nutrient, but knocking out the VNN-1 pathway in mice causes a deficiency in other compounds synthesized in this area. In the researchers' current animal study, they are testing how supplementing the mice with those compounds may affect how they respond to corticosteroid treatment for asthma.