The University of Texas Health Science Center at Tyler (UTHSCT) researcher Dr. Sreerama Shetty, a cellular and molecular biology professor, has received a two-year Department of Defense (DoD) grant for nearly $300,000 to continue research on a novel intervention therapy he and his research team have developed for a COVID-19-related lung disease.
“Our research has a strong potential of yielding a new, safe, convenient and effective intervention for patients with COVID-19 due to infection caused by coronavirus 2 (CoV-2),” Shetty said. Patients with acute lung injury (ALI) from COVID-19 often die due to acute lung inflammation that can lead to alveolar damage and organ failure. The CoV-2 targets ACE-2 proteins lining the surface of human cells, including the alveolar cells in the lungs, causing ALI and alveolar epithelial cell death and lung scarring, making a lack of air exchange life threatening.
Shetty’s research identified a specific peptide, called LTI-03 (also called CSP7), that inhibits alveolar epithelial cell lung injury, including ALI due to sepsis.
“LTI-03 is well tolerated, can be delivered systemically or via the airway in liquid formulation or micronized dry powder form,” Shetty said. “We believe LTI-03 can mitigate ALI associated with COVID-19. Our research will test the efficacy of systemically and airway-delivered LTI-03 against alveolar epithelial cell damage and acute lung injury.”
Shetty’s research will determine whether systemically delivered LTI-03 improves overall survival by inhibiting ALI due to CoV-2 infection and will determine whether better efficacy is achieved by airway inhalation using standard lung function, CT imaging, blood oxygenation, lung viral load, biochemical and histological markers and survival endpoints.
“Our grant proposal caters to the aggregate strengths of the team in drug discovery, formulation, airway delivery and virology,” Shetty said.
LTI-03 could be a potential treatment for chronic lung disease called idiopathic pulmonary fibrosis (IPF) that causes progressive lung scarring primarily in adults age 65 and older. With no known cure, fatality is generally three to five years following diagnosis. LTI-03 administered as an inhalant is entering clinical safety trials in Ireland and could cause a worldwide paradigm shift in the treatment of lung fibrosis.
“If the clinical trials are successful, LTI-03 as an inhalant could become the signature career work of my lifetime,” Shetty said.
Initial evidence suggests that LTI-03 reverses lung fibrosis in multiple preclinical models, including human IPF tissues, reduces fluid buildup in the lungs that causes life-threatening pneumonia and restores the survival of damaged lung lining cells. IPF causes about 40,000 deaths annually.
Antifibrotic drugs approved in 2014 to treat IPF only decelerated the progression of fibrosis, buying patients more time, but LTI-03 as an inhalation therapy holds promise to return patients to healthier lung function by sustaining the survival of damaged lung lining cells and targeting a different cellular signaling pathway than previous pharmaceutical approaches.
UTHSCT attracts some of the top researchers from around the world to its 150,000-square-foot research facility in Tyler, Texas, where new medications, protocols and cures are developed. Researchers have earned nearly $300 million in grant-funded research to offer hope to patients in need.