Peripheral Blood-Based Proteinomic Test for The Diagnosis of Idiopathic Pulmonary Fibrosis (IPF)

SUMMARY

• The current clinical standards for diagnosing idiopathic pulmonary fibrosis (IPF) include lung biopsies and radiographic examination, which cannot reliably discriminate between IPF patients and those with similarly presenting lung diseases. 
• The inventors used a multianalyte protein system to assay levels of 49 plasma proteins in a cohort of 74 IPF patients and 53 control patients. The inventors demonstrated that relative levels of the proteins: MMP7, IGFBP1, and TNFRSF1A can be used to delineate between IPF patients, healthy patients, and patients with similarly presenting lung diseases. The elevated levels of these proteins are localized to the lung microenvironment and are secreted by the alveoli, and are mechanistically associated with IPF disease progression.
• The invention is a method of diagnosing IPF patients using expression of a panel of proteins in the peripheral blood. Relative protein expression levels can be assayed by serum mRNA quantification.
• In proof-of-concept experiments, the diagnostic was validated on a separate retrospective cohort from which it was derived (N=53) and was shown to have a sensitivity of 98.6% and a specificity of 98.1%. The diagnostic was also shown to differentiate patients with IPF from those with similarly presenting hypersensitivity pneumonitis with a sensitivity of 96.3% and a specificity of 87.2%. Moreover, serum concentration of MMP7 was used as an endpoint in a multi-institution phase II clinical trial ran by the inventors.

FIGURE

ADVANTAGES

ADVANTAGES

• Robust discrimination between IPF and other lung diseases
• Non-invasive diagnostic method
• Eliminates need for multiple successive tests
• Used as endpoint in phase II clinical trial

APPLICATIONS

• IPF diagnosis and patient stratification
• Clinical trials enrolment and monitoring
• Lung transplant listing

PUBLICATIONS

• Rosas, IO; et al. MMP1 and MMP7 as potential blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med. 2008 Apr 29;5(4).
• Rosas, IO; et al. A phase II clinical trial of low-dose inhaled carbon monoxide in idiopathic pulmonary fibrosis. Chest. 2018 Jan; 153(1):94-104.

Nov 14, 2019

Licensing

Clinically validated|Used as endpoint in phase II trial (NCT01214187)

Patent Issued

Imre Noth

• US: 8,846,341