Sunday, August 14, 2016

"Regeneration Intelligence" For Diagnosis of Lung and Liver fibrosis and Glaucoma

Collaboration of Insilico Inc. with Atlas Regeneration Inc, Vision Genomic Inc and Howard University has given two high impact papers to explain use of newly developed Regeneration Intelligence tool for the identification of perturbation in pathways of lung and liver fibrosis and glaucoma. It can be used as diagnosis tool for the fibrosis that is often mis-diagnosed.

A) Lung and Liver Fibrosis

Fibrosis is a age related condition that is marked by the accumulation of extracellular matrix that occurs in wide range organs. This leads to changes in the structural and functional properties of organ that leads to pathological conditions. Lungs and liver are the most commonly affected by fibrotic situation leading to development of idiopathic pulmonary fibrosis (IPF) and hepatic fibrosis.

Figure 1 a - c
The figure 1 a) & b) shows venn diagram of common pathway up-regulated and down regulated respectively for lung and liver fibrosis c) venn diagram d) PAS values for 20 common signaling pathway of lung and liver fibrosis

By their new Regeneration Intelligence algorithm they were able to pin down to TFG-beta, IL6 and ILK signaling pathways, which were found to be conserved in fibro-genesis. The software provides a validated mathematical frame work for assessment of signaling pathway alteration that drives the fibrosis in organs like lungs and liver.

This work supports a theory that conserved signaling elements may shared by various fibrotic organs. It provides a new evidence that evolutionary conserved pathways can be used as therapeutic drug targets. The work was highlighted in Eureka Alert Science Magazine and Business Standard news letter. The scientific paper can be downloaded from this here.

B) Glaucoma 

Glaucoma is also kind of fibrotic condition. Primary open angle glaucoma (POAG) is most common form of glaucoma that is characterised by free aqueous humor (AH) outflow and logging between iris and cornea that do not get drained from trabecular meshwork (TM) due to clogging of the channels.  This causes damaging effect on the mesh like Lamina Cribrosa (LC) through which optic nerve bypass. They have used a software suite, AMD medicine to understand the molecular pathway that causes the accumulation of AH and prevention of its outflow by carrying out intracellular signalling pathway activation (SAP).                           Accepted paper can be found here

Figure 2:  It shows the pathology of formation of glaucoma due to increase intra ocular pressure due to blockage in the removal of AH. A) shows TM and optical nerve head containing TC. B) shows TM located between cornea and iris. It shows that AH produced by ciliary body is moved towards anterior end shown by arrows and expelled into schlemm's canal via TM.  C) shows flow of AH into schlemm's canal through juxtacanaliular tissue. AH outflow is blocked due to clogging in TM leads to increase in intra ocular pressure. D) Optic nerve head containing axon of RGC and lamina cribrosa structure. E) shows morphology of collagen fibres of lamina cribrosa. F) SEM trabecular meshwork and G) SEM of lamina cribrosa.

They have found that  TGF-beta causes activation of pro-fibrotic pathway in TM and LC. This activated pro-fibrotic pathway causes extracellular matrix re-modelling in TM and LC. This makes TM less efficient in draining the AH. This causes LC more susceptible to damage due to increase intra ocular pressure caused because of increased AH. They propose molecular pathways that could be used for developing therapeutic intervention against glaucoma. The significance of the finding was recently discussed Eureka Alert Science Magazine and Medical News. These two papers shows a proof principle that there are some common age related signalling pathways that are shared by organs. Regeneration Intelligence based mathematical frame work gives an opportunity to explore this tool towards study of common signatures for age related fibrosis in other organs of human body. This may give us an opportunity to design an effective therapeutic strategy to fight age related disease like fibrosis.