CEO Lisa Patel discusses our approach to tackling chronic disease.

“Nearly every human malady … damages tissues, and 45% of all deaths can be traced to inflammation- and fibrosis- related regenerative failures (1)”. These are the opening thoughts from a recent perspective in Science Magazine on how we can coax tissues to regenerate. If we could achieve this goal, we might certainly impact that 45% of deaths and potentially make the quality of those saved lives better.

The article describes how identifying instructive cues that direct refractory tissues down a regenerative path is a critical, but elusive, goal because of three main roadblocks:
1. Insufficient/functionally inadequate progenitor cells
2. Fibrosis
3. Chronic inflammation

Of course, there’s lots of work underway to try and address each of these problems, and some progress being made in each. For example, various stem cell approaches are being trialled for skin wound healing and type I diabetes. Unfortunately though, these approaches are beset by complicated problems, not least how we direct the cells to the right place and then get them to connect to what’s already there.

But what’s not often considered is how important it is to ensure that we support the inflammation we need to help repair whilst controlling the aberrant, chronic inflammation that prolongs disease. For example, in inflammatory bowel disease, where a multitude of issues such as prolonged immune responses, defective epithelial repair, and movement of bacteria into underlying tissue, drive progression, supplying intestinal stem cells to the patient without controlling their inflammation, at best offers only a temporary patch.

Of course, this presents a major hurdle, because many of the factors that we target to control inflammation are also involved in promoting repair. TNF⍺, for example, is a key driver of inflammation in rheumatoid arthritis, but also critical in kickstarting repair. So, when we treat with TNF blockers, we control symptoms…but importantly, we prevent repair from occurring too.

So, what do we need to get in place to unlock a regenerative response? Firstly, we would carefully control inflammation, but leave the repair-inducing drivers in place. Secondly, we would unlock our endogenous regenerative capacity. In that regard, several rather interesting lines of evidence indicate that adult organs may still possess molecular roadmaps to activate regenerative responses. And thirdly, we would need to ensure that tissue remodelling proceeded normally, without going to fibrosis (scarring). If we could do these three things, what could the consequences be? Perhaps we could effectively, repair and regenerate damaged tissue?

At Istesso, we call this programmed disease resolution. We believe it would take us from disease modification to disease resolution. It’s a big goal, but we think preventing up to 45% of deaths might just be worth it.