Asthma, Author Interviews / 26.05.2013
Inhibition of Sphingolipid Synthesis Produced Asthmatic Lungs, without Inflammation
MedicalResearch.com eInterview with: Stefan Worgall Ph.D., M.D
Department of Genetic Medicine and 4Department of Pediatrics
Weill Cornell Medical College,
New York, NY 10021, USA.MedicalResearch.com: What are the main findings of the study?
Dr. Worgall: Asthma is a common disease and large genome-wide association studies found variation in the gene for ORMDL3, in to up to 30 percent of asthma cases. The over-production ORMDL3 was connected to childhood asthma. ORMDL3 protein inhibits the new production of sphingolipids. Our study connects sphingolipid metabolism mechanistically to human asthma for the first time. We found that inhibition of the enzyme that is critical to sphingolipid synthesis, serine palmitoyl-CoA transferase (SPT), produced asthmatic lungs in mice and in human bronchi, as it did in mice that had a genetic defect in SPT. When these mice were given methacholine their airways constricted further. We further determined that the airway hyperactivity seen in the mice was not linked to increased inflammation, which is a target for most asthma therapies.





