While fibrosis can represent a normal physiologic process, aberrant fibrosis is a pathology that occurs in many different serious disease states. If left unchecked, this excessive and uncontrolled scar tissue formation can have devastating consequences, including destruction of normal tissue architecture, organ dysfunction, and, in many cases, organ failure and death. The pathobiology of fibrosis can vary across different diseases, but there are commonalities in fibrogenic processes that represent attractive points for therapeutic intervention.
In groundbreaking work published in Nature Medicine, Indalo’s co-founders elucidated the central importance of specific integrins (heterodimeric transmembrane proteins that mediate cell-cell and cell-matrix interactions) in promoting fibrosis. Expression of many integrins is elevated in fibrotic lesions, with a unique constellation displayed on different cell types. Indalo is targeting a subset of integrins expressed on epithelial cells and fibroblasts that recognize the Arg-Gly-Asp (RGD) sequence in cognate ligands. These RGD-binding integrins have been implicated in perpetuating shared fibrogenic processes in different diseases.
The pro-fibrotic role played by RGD-binding integrins is demonstrated by the profound antifibrotic effects achieved through their genetic depletion and pharmacologic modulation in preclinical models. Collectively, these results suggest that selectively targeting key RGD-binding integrins may represent an attractive therapeutic strategy for treating serious fibrotic diseases.