A research team at Cincinnati Children’s Hospital Medical Center has received a $150,000 grant to repurpose Barasertib as a potential treatment for Idiopathic Pulmonary Fibrosis. Using a computational drug discovery pipeline coupled with preclinical validation studies, Anil Jegga, DVM, MRes, of the Division of Biomedical Informatics, and Satish Madala, PhD, of the Division of Pulmonary Medicine, identified aurora kinase B (AURKB) as a lead target and AURKB-selective inhibitor Barasertib as a lead small molecule for IPF.
Barasertib, a Phase I/II drug with potential anti-cancer activity, is known to have systemic exposure-related side effects. The pilot study will test an inhalation route to administer Barasertib for direct delivery to the lungs. This non-systemic route of administration will potentially improve the therapeutic index and minimize side effects. The grant is funded through the NIH Center for Accelerated Innovations at Cleveland Clinic (NCAI-CC) and the Center for Technology Commercialization at Cincinnati Children’s Hospital Medical Center.
Idiopathic Pulmonary Fibrosis (IPF) is an irreversible disease that results in scarring of lung tissue and loss of lung function. With a 5-year survival rate of 30-50%, it is the most fatal interstitial lung disease. Esbriet (Pirfenidone) and Ofev (Nintedanib) are two recently FDA-approved drugs to treat IPF. These drugs slow the rate of decline in lung function, but they do not halt progression or reverse fibrosis.
The Jegga and Madala research team found that Aurora Kinase B (AURKB) functions as a positive regulator of pulmonary fibrosis, causing excessive proliferation and survival in fibroblasts. Inhibiting AURKB activity could decrease fibroblast activation and lead to improved treatments for IPF.
Barasertib is a highly selective AURKB inhibitor that can prevent the progression and reverse fibrosis in mouse models of pulmonary fibrosis. However, since IPF requires prolonged treatment, the known systemic exposure-related side effects of Barasertib are not ideal.
The targeted therapeutic pressurized aerosol delivery method of Barasertib tested in this study can be given in smaller doses compared to systemic treatment. The inhaled therapeutic could have rapid onset of drug action with lesser side effects. Researchers aim to determine the optimal aerosol formulation and dosage of Barasertib dry powder for treatment of pulmonary fibrosis.
If the safety and efficacy of directly delivering Barasertib into airways is determined, the culmination of this work could enable future innovative IPF clinical trials using the drug. New therapies that inhibit fibroblast activation to reverse established and ongoing fibrosis would improve the current standard of care for IPF.