Novel Biomarker for Diagnosis and Treatment of Chronic Lung Diseases

This invention is a targeted method of treating conditions associated with aberrant L1 expression, including cancers. The method involves determining the expression levels of L1 in a patient and then administering a known TGF-β1 inhibitor. Further, the invention acts on the discovery of an underlying mechanism of aberrant L1 expression that will allow for drug discovery, biomarker validation, and assay validation for L1 related diseases. 

Background:
Transforming growth factor beta 1 (TGFb1) is necessary to mediate the oncogenic phenotype induced by B(a)P activation of LINE-1. B(a)P is an environmental carcinogen. ORF-1 protein (translated from LINE-1 mRNA) is correlated with a pre-oncogenic phenotype in smokers with Chronic Obstructive Pulmonary Disease (COPD). Products that inhibit TGFb1 and LINE-1 will improve cancers and diseases where LINE-1 activation is the cause of the dysregulation.

Applications:

• Platforms for the use of LINE-1 in treatment and diagnosis of diseases
• Diagnostic biomarkers for COPD and lung cancer
• Immunoassays for ORF1 in blood, liquid biopsy, fresh and fixed tissue 
• Algorithms enabling clinical decision making with ORF-1 and ORF-2, or LINE-1 sequence information
• DNA sequence-based decision rules for genetic material obtained from blood, liquid biopsy, fixed tissue
• DNA probes (in situ hybridization, chromosome paints) for LINE1 polymorphs from genetic material obtained from blood, liquid biopsy, and fixed tissue
• Expression assays of LINE-1 (in situ hybridization, microarrays, RNAseq, RT-PCR in blood, liquid biopsy, fresh and fixed tissue)
• Natural products with medicinal properties
• Newly discovered drugs designed to inhibit aberrant LINE-1 activation

Advantages:

• May meet the unmet need for the detection and treatment of lung cancer and other chronic lung diseases
• Sinks and traps decoy receptors and binding proteins that sequester TGFb1 (activin receptor-like kinases)
• Can utilize TGF beta inhibitors to inhibit the expression of LINE-1 for treatment of COPD and other lung related diseases
• Provides an expansive platform