Software Detects ‘Molecular Signatures’ in Development of Lung and Liver Fibrosis

A collaborative research effort identified new pathways involved in fibrosis using a software tool known as “Regeneration Intelligence,” which evaluated perturbations in several signaling pathways in lung and liver fibrosis, and in glaucoma.

The research, leading to two studies, was conducted by Insilico Medicine working with scientists at Atlas Regeneration, Vision Genomics, and Howard University.

The first study, “Common pathway signature in lung and liver fibrosis,” published in the journal Cell Cycle, may promote the development of new tailored therapies that target components of these signaling pathways in patients with fibrosis.

“Fibrosis is one of the age-related pathologies that disrupt organ functionality dramatically,” Eugene Makarev, PhD, vice president of pathway analytics at Insilico Medicine, said in a press release. “Currently, there are no approved anti-fibrotic remedy and no reliable fibrotic biomarker. ‘Regeneration Intelligence’ … can detect hidden fibrotic molecular signatures based on a pathway network analysis. The system can identify specific fibrogenic molecular changes regardless of detecting platform and tissue of origin.

“Despite many efforts, fibrosis if often misdiagnosed. Our system is supposed to help with proper and timely diagnostic,” Makarev said.

Researchers tested 32 patients with fibrotic liver and 13 patients with idiopathic pulmonary fibrosis (IPF) using Regeneration Intelligence, which allowed them to identify pathways not previously associated with fibrosis. This approach resulted in the selection of small molecules and natural compounds that could reduce the differences in signaling pathway activation observed between healthy and fibrotic tissues.

In the second study, “Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma,” also published in Cell Cycle, Regeneration Intelligence was used to identify disrupted pathways in glaucoma, an eye disease characterized by increased intraocular pressure.

Results showed that increased levels of TGFβ in glaucoma-affected tissues led to the activation of pro-fibrotic pathways, which may lead to increased damage from elevated intraocular pressure.

“We are very excited to continue our collaboration with Insilico Medicine,” said Antonei Csoka, PhD, CEO of Vision Genomics. “Using the innovative ‘Regeneration Intelligence’ software, we have discovered previously-undetected pro-fibrotic signatures in glaucoma, based on pathway analysis. This new knowledge will allow Vision Genomics, Insilico Medicine and Howard University to cooperatively select and develop anti-fibrotic small molecule interventions to minimize or reverse this fibrotic state, and restore the tissue to normal function.”