A researcher at Case Western Reserve University (CWRU) in Cleveland, Ohio, was awarded a five-year, $13.3 million federal grant to fund the development and testing of personalized medication combinations tailored to address the needs of children with cystic fibrosis (CF) and severe asthma.
The first major study of its kind is being led by principal investigator Dr. Benjamin Gaston, MD, chief of the Division of Pediatric Pulmonary, Allergy and Immunology and professor of pediatric medicine at Case Western School of Medicine and University Hospital’s Rainbow Babies & Children’s Hospital.
“While there are a number of medications used to treat these conditions, until now they have not been combined in large numbers of patients with an aim of discovering which combinations work best for specific disease profiles. 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 in a press release.
“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. The investigators anticipate that this approach will be adopted over time by other pediatric medical centers throughout the country and around the world,” he added.
Gaston’s team at CWRU studies cysteine modifications downstream of nitric oxide synthase (NOS) activation, which are mechanisms relevant to CF, asthma, pulmonary arterial hypertension (PAH), and apnea.
The grant, titled “Personalized small molecule therapy for severe asthma and cystic fibrosis“ from the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI), will fund Gaston and his colleagues’ research in conducting highly specific lung function testing and laboratory analyses to identify patients most likely to respond to particular therapies.
The multidisciplinary program funded by the NHLBI grant is based on drug development, clinical drug trials, cell culture, cell physiology and genetics, and airway redox chemistry.
The goal of this research is to develop personalized combinations of medications for patients with severe airway diseases. Varying combinations of medications will be assessed, and it is hoped that new treatments can be discovered, in part by the lead investigators.
“It is now clear from our work and that of others that there is substantial clinical heterogeneity in both severe asthma and CF, and that there are specific patients who will and will not respond to each treatment,” the researchers wrote in the study’s abstract. “As with most drugs, patients who are non-responders could actually be harmed by unnecessary treatment.”
“We have now developed noninvasive or minimally invasive biomarker approaches to identify responders and non-responders to specific treatments,” they wrote, noting that “many severe asthma and CF patients are benefiting already from personalized biological and small molecule therapies that have recently been developed; our proposed program is meant to complement these novel therapies in order to optimize the ease and efficacy… and minimize the cost — of treatment for each patient.”
The Case Western release explains that researchers will assess patients’ airway-cell pH levels. Low pH levels are frequently observed in patients with severe asthma and CF, and the researchers will be able to determine which combinations of medications (pH modifiers) work best in these patients, for instance whether inhaled albuterol (a bronchodilator) in buffered glycine is more effective than albuterol as a monotherapy.
Another of the project’s research goals is to grow individual patients’ cells in the laboratory and treat them with various CF corrector agents. This process would identify the most effective therapy or combination of therapies in addressing dysfunction in the cell system, and could ultimately be used to improve patients’ lung function.
In addition to Gaston, CWRU investigators include project leaders Dr. Jonathan Stamler, MD, director of the Harrington Discovery Institute at UH; Mitchell Drumm, PhD; as well as core directors Dr. 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. “My colleagues and I are grateful to the Institute for its support and honored by their faith in our capacity to translate new scientific discoveries into therapies for these patients.”
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