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Repurposing of Reverse Transcriptase Inhibitors to Alleviate TLR5-mediated Inflammation in Cystic Fibrosis
Anti-inflammatory therapy targeting TLR5 to provide therapeutic cystic fibrosis relief, through repurposing reverse transcriptase inhibitors
Background
- Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CF transmembrane conductance regulator (CTFR) gene
- This hereditary mutation results in inadequate mucus production and compromises bacterial clearance mechanisms, predisposing CF patients to persistent lung infections
- To fight bacterial infections, cells express TLR5 in response to bacterial motor protein Flagellum (FLA), which causes an innate immune response
- Unregulated TLR5 activation in response FLA results in pathogenic inflammation
- Most notably, P. aeruginosa can cause a life-threatening infection in the pulmonary tract of CF patients by triggering excess TLR5-mediated inflammation
- Unmet Need: Anti-inflammatory therapy targeting TLR5 to provide therapeutic relief that does not drive immunotoxicity
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