Home Manchester University of Manchester technology to aid development of anti-fibrotic drugs

University of Manchester technology to aid development of anti-fibrotic drugs

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Karl Kadler

Professor Karl Kadler and his team have developed technology which has the ability to monitor, quantitate and observe new collagen synthesis, on the background of existing collagen and under normal genetic control.

Currently, there are no drugs on the market that regulate collagen.

Professor Kadler comments: “Research into finding a treatment of fibrosis can benefit the most. There are no current therapies for fibroproliferative disease, which can affect any organ system leading to death and is a complicating factor in 45% of all deaths including cancer.

“Collagen is very strong and forms bone, cartilage, skin, and tendons,” continues Professor Kadler.

“Collagen fibrils, which account for 30% of the mass of vertebrates and are the mechanical framework for all fibrous and hard tissues, as well as organs such as skin, gut and muscle – are also the end-point of fibrosis (e.g. of heart, lung, liver, skin and kidney) in which functional tissue is replaced by collagen that shouldn’t be there.”

He added, “As a simple analogy, think of collagen as the walls in a building; they are essential for holding up the roof and giving the building its shape and strength but additional walls cutting across rooms and corridors makes the building unusable.  Too much collagen in lungs, heart and liver stops these organs from working”.

“We want to understand how and where collagen fibrils are assembled with the aim of controlling this process in the treatment of fibrotic disease.”

The solution appears simple, let’s find a way of stopping our bodies making too much collagen, but it isn’t that easy.  Professor Kadler suggests, “Understanding how collagen is produced, processed and regulated by cells is key to the development of new treatment strategies, however it is currently impossible to quantitatively image the process. The hurdle to overcome is to visualise new collagen (the fibrotic, bad collagen) on top of the existing (good) collagen.  Our approach allows us to visualise the new collagen in the presence of existing collagen in the presence of candidate anti-fibrotic drugs.

Explaining the technology, he said: “We have used the latest genome editing technology to integrate a photo switchable marker in the collagen protein. This does not disrupt the endogenous wild type regulation of collagen, but the photo switchable nature of this marker allows us to differentiate newly deposited collagen from previously deposited collagen.

“This is achieved by simply exposing the cells to a specific wavelength of light. This platform allows the quantitative study of collagen production in health and disease as well as the evaluation of modulators of collagen production with potential anti-fibrotic use.”

Professor Kadler said the technology “is the first tool to measure new collagen synthesis in the fight against fibrosis.”