Description:

TREM1, HMBGB1 and PGLYRP1 Antagonism: Therapeutics for Severe and Neutrophilic Asthma in Horses and Humans

Overview of Technology

Therapeutics for severe and neutrophilic asthma in horses and humans

Background of Technology

HMBGI signaling, TREM1 expression and signaling and PGLYRP1 expression are all increased in the lung biopsies of horses with severe/neutrophilic asthma exacerbation. Increases in HMGB1 and TREM1 have also been identified in association with severe and neutrophilic human asthma. In line with findings that antagonism of TREM1 and HMGB1 improve models of sepsis, which is also a severe inflammatory disease with a predominance of neutrophils, by extension these findings support the utility of TREM1 and HMGB1 antagonism to treat/moderate severe and neutrophilic asthma. In addition, because PGLYRP1 is a ligand for TREM1, neutralization of PGYLYRP1 should similarly limit signs of neutrophilic asthma in a manner analogous to TREM1 antagonism.

Technology Description

Mississippi State researchers’ data in horses with severe/neutrophilic asthma indicate abnormal innate immune responses are driving this type of asthma. These findings fill a gap by corroborating findings in severe/neutrophilic human asthma that have been gained through non-invasive methods. These methods don’t provide as comprehensive an evaluation of what is happening in the lung as this biopsy-based analyses. There is also evidence of these pathways in certain mouse models, but mouse models don’t fully recapitulate the complexity of human asthma.

These results provide strong corroborative evidence that these signaling pathways are conserved across evolutionary clades within the lung tissue from horses to humans with neutrophilic asthma, providing support that these pathways are relevant to the pathology of severe and neutrophilic asthma.

Benefits

This information improves upon the prior art because there is a lack of understanding of the pathophysiology of severe and neutrophilic asthma along with a well-recognized need for therapeutics to address this human asthma cohort. It is not possible in humans to perform invasive approaches such as the serial lung biopsy sampling that was performed on horses with naturally occurring neutrophilic asthma. Yet these invasive approaches, which can determine the genes that are being expressed during exacerbations in neutrophilic asthma are exactly what is needed to identify new and appropriate therapeutics.

Applications

The commercial value of this invention is that it implicates three lines of therapy to address severe and neutrophilic asthma in humans.

Opportunity

This innovation is in the basic research stage and can be used to help develop into testable models/products.