AdamTS4 inhibitor for respiratory infection (SJ-20-0025)

St. Jude Reference #SJ-20-0025

Description

Severe respiratory infections can result in acute respiratory distress syndrome. There has been no effective pharmacological therapeutics shown to improve outcomes for patients with acute respiratory distress syndrome. Treatment strategies are supportive, involving mechanical ventilation and control of fluid intake. Although the host inflammatory response is required to limit the spread of and eventually clear the pathogen, immunopathology is also known to be a major contributor to tissue damage. 

Researchers at St. Jude demonstrated that respiratory viral infection creates multiple fibroblast populations, which they termed ECM-synthesizing, damage-responsive, and interferon-responsive. They found the damage-responsive population drives lethal immunopathology during severe influenza virus infection. A therapeutic agent that targets the matrix protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.  

Researchers at St. Jude have invented a formulation of a specific inhibitor of the enzyme Adamts4 (a disintegrin and metalloproteinase with thrombospondin motif) with one of several broad spectrum antibiotics which could be used to treat respiratory infections by unknown pathogens, or by known viral pathogens without effective treatment, or by any pathogen that induces excess levels of Adamts4 activity.

An additional formulation could include the combination of Adamts4 with oseltamivir and/or baloxivir and/or an antibiotic for treatment of influenza specifically with concern for secondary bacterial infection.                          

This invention would prevent lung damage, rather than just targeting the pathogen. Most deaths from respiratory infection in otherwise healthy individuals are not due to lack of control of the pathogen, but rather longer-term consequences of lung damage. 

Keywords

Severe respiratory infection, acute respiratory distress syndrome, viral infection, multiple fibroblast populations, ECM-synthesizing, damage-responsive, interferon-responsive, influenza, Adamts4, oseltamivir, baloxivir, secondary bacterial infection, prevent lung damage.

Granted patents or published applications

Pending international application published as WO 2021/214637

Related scientific references

A press release about the Nature article: https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/research-advances-understanding-of-life-threatening-lung-inflammation-following-the-flu.html

The Nature article: 
Boyd, D.F., Allen, E.K., Randolph, A.G. et al. Exuberant fibroblast activity compromises lung function via ADAMTS4. Nature (2020). https://doi.org/10.1038/s41586-020-2877-5 or https://www.nature.com/articles/s41586-020-2877-5#citeas

Licensing opportunities

More information is available under a confidentiality agreement.
Contact: chad.riggs@stjude.org

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.