A research team at Cincinnati Children’s Hospital Medical Center has received a $626,000 grant to test saracatinib (AZD0530), an experimental drug,  as a new potential treatment for cystic fibrosis (CF). The grant will support further preclinical evaluation of this new candidate drug, which promises to compliment current therapies. It could offer under-treated cystic fibrosis populations greater access to therapy and directly address infection and inflammation associated with the lung disease.

The team is being led by Anil Jegga, DVM, MRes, professor in the Division of Biomedical Informatics, Anjaparavanda Naren, PhD, professor in the Division of Pulmonary Medicine and Director of the Cystic Fibrosis Research Center, and John  Clancy, MD, professor in the Division of Pulmonary Medicine.

Images of Anil Jegga, DVM, MRes, Anjaparavanda P. Naren, PhD and John Clancy, MD
(From left) Anil Jegga, DVM, MRes, Anjaparavanda P. Naren, PhD and John Clancy, MD are evaluating a potential cystic fibrosis treatment that was initially identified through computational analyses.

Cystic fibrosis, a hereditary disorder, affects more than 30,000 individuals in the United States and 70,000 individuals worldwide, with an annual healthcare cost of over $1.8 billion. It is a progressive genetic disease in which a defective gene causes a thick, sticky buildup of mucus in the lungs, pancreas and other organs. Over time the disorder limits a patient’s ability to breathe.

The CF community has benefited from some recent drug advances but the efficacy of these new drugs can be undermined by persistent airway infection and inflammation in CF patients. Furthermore, these drugs are extremely expensive. Hence, providing new and effective therapeutics continues to be a critical need in the CF community.

Computational Drug Repurposing

Jegga is an expert in systems biology and computational drug repurposing, which relies on developing and applying computational analyses to discover new uses for existing drugs or investigational small molecules.

“We are working to make this process ‘systematically serendipitous’ thanks to the volume of multifaceted biomedical and genomic big data now available”

–Anil Jegga, DVM, MRes

He conducted a combinatorial bioinformatics analysis of CF patient gene expression data coupled with compound screening to identify saracatinib (AZD0530), an experimental drug that has already been tested for safety in hundreds of human patients, as a candidate therapeutic for CF.

Preliminary testing in the Naren Lab confirmed this finding using enteroids, which are artificially grown masses of cells or tissues generated from CF patients that allow new compounds to be tested on those tissues safely outside the body. Several prior studies have also demonstrated the anti-inflammatory and anti-infective activity of saracatinib.

Diagram depicting data repurposing workflow that resulted in the identification of saracatinib (AZD0530) as a potential treatment for cystic fibrosis.

“Most approved repositioned drugs were discovered accidentally,” Jegga says. “We are working to make this process ‘systematically serendipitous’ thanks to the volume of multifaceted biomedical and genomic big data now available; the computing power at our disposal; and the sophisticated data-mining and data-driven algorithms and approaches that help predict novel indications for approved drugs or late-stage investigational compounds.”

Project Goals

The new grant project aims to determine if saracatinib is a candidate therapeutic for CF and to identify its primary mechanism of action relevant to CF lung disease. Th team will also evaluate the effect of saracatinib on infection and inflammation associated with CF and prepare for a clinical trial to test effectiveness of saracatinib for CF therapy. The ultimate goal of this project is to provide evidence in support of a multi-center clinical trial of saracatinib in CF.

The project team also includes John J. Brewington, MD, whose research work includes personalized model systems to predict and study drug benefit for an individual patient and Lin Fei, PhD, of the Division of Biostatistics and Epidemiology.

This two-year grant is funded through the National Center for Advancing Translational Sciences, part of the National Institutes of Health.

For more on the grant, please visit Preclinical Characterization of Saracatinib for Cystic Fibrosis Therapy. Read more about Anil Jegga’s research here, here and here.

Computational Analyses Lead to Grant for Potential Cystic Fibrosis Treatment
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