The National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has granted a five-year, $13.3 million award to Benjamin Gaston, MD, to lead a research program aimed at translating new, small molecule drugs into personalized combination therapies for children with severe asthma and cystic fibrosis (CF).
The research project is titled “Personalized small molecule therapy for severe asthma and cystic fibrosis.”
Gaston is a pediatric pulmonologist and researcher at Case Western Reserve University School of Medicine and Rainbow Babies & Children’s Hospital. He will be leading the new research program with Jonathan Stamler, MD, director of the Harrington Discovery Institute at UH; Mitchell Drumm, PhD; Michael Konstan, MD; Ted Torphy, PhD; Calvin Cotton, PhD; and Mark Schlucter, PhD.
“This is a bold step by the National Heart, Lung and Blood Institute to change the way we think about cystic fibrosis and severe asthma treatment,” Gaston said in a news release. “My colleagues and I are grateful to the Institute for its support and honored by (the NHLBI’s) faith in our capacity to translate new scientific discoveries into therapies for these patients.”
At Case Western Reserve University’s pediatric and internal medicine research programs, Gaston and colleagues have developed small molecule therapies for both asthma and CF. These therapies, including S-nitrosoglutathione (GSNO), GSNO-mimetic compounds and GSNO reductase inhibitors are potentially effective to treat both conditions. However, severe asthma and CF have substantial clinical heterogeneity, and some patients respond to therapies while others do not.
In the new research program, the team will combine drugs and test these combinations in large numbers of patients to understand which work best for specific disease profiles. The team hopes this combination approach will be adopted eventually by other national and international pediatric medical centers.
Researchers will perform highly specific lung function testing to identify which patients will or will not likely respond to their proposed therapies. These include assessing patients’ airway-cell pH levels. In patients with a low pH, researchers will determine which drug combinations (“pH modifiers”) are more effective. For instance, if inhaled albuterol (a bronchodilator) in buffered glycine is more effective than albuterol alone.
Then the team will begin personalized clinical trials using specific clinical testing and selection criteria developed in the first cycle. Researchers will grow individual patients’ cells in the lab, and treat these cells with different CF corrector agents. The most effective therapy or combination of therapies in the cell system may be used to improve patients’ lung function.
“Cells of cancer patients can be studied for response to different agents and combinations of agents in order to identify the best treatment approach,” Gaston said. “Here, we will take a similar approach to individualize therapy for severe airways diseases. The focus of our project is personalized medicine: identifying the most synergistic treatment method for each patient based on their own needs,” he said.