Wound-healing bacteria

26 March 2019

Interview with 

Evelina Vågesjö, Ilya Pharma

BACTERIA-ARTIST-IMPRESSION

Artist impression of bacteria

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It sounds counterintuitive to rub bacteria into a wound to make it heal faster, but a Swedish startup, called Ilya Pharma are doing just that, with astonishing results. A few years ago, during her PhD, Evelina Vågesjö discovered a family of immune signals made by white blood cells that lure other immune cells into wound sites where they can promote repair. But these signals are tricky to produce, and they act for only a very short time. Her solution was to add the gene used in the body to make the immune signal to bacteria like those you find in yoghurt and apply the modified bacteria into the injury…

Evelina - During my PhD I investigated different molecules that immune cells use to talk to each other so that they know how to move around in the body, and especially if we get an injury I specialised in a molecule that is increased in the concentration at the injured site. So what we could actually do is to boost the process at an earlier stage and then the whole healing is faster and this we have described in animals -  mice and mini pigs but we weren't quite happy with that and we want to find out if this also works in humans, so that's the next step. So we're going to do a trial in healthy volunteers is the next step.

Chris - What is the class of molecules that you've discovered that do this?

Evelina - They are called chemokines. Essentially what they do is tell immune cells how to move in the body. So they build up gradients from a high concentration to a low concentration and then the immune cells move along this gradient.

Chris - So it's a bit like the immune cells are smelling this trail, like a breadcrumb I suppose - Hansel and Gretel breadcrumb trail of where the wound is and they sniff out the wound and flock in, and you're saying if I add extra of this molecule really early into the wound I can get many more immune cells there much more promptly so I can kickstart the wound healing?

Evelina - Yeah, that's exactly how I would describe it. By forcing the wound to secrete more of this we can get much more efficient immune cells to come there earlier and accelerate the healing process.

Chris - But these chemicals, these chemokines, they're complicated, they're proteins they're not just something that you can knockout easily so how are you making the wound make that?

Evelina - These chemokines, they have a very short half life so if you are just taking the chemokine and add it to the wound it will be degraded very fast. So we have overcome this by asking a type of lactic acid bacteria to produce this for us in the wound. We took normal probiotic bacteria found in yoghurt and then we inserted a gene into them that express this human chemokine, and then when they are in the wound they produce this chemokine for about one hour to the wound's surface and that is enough to activate the immune cells.

Chris - So you're saying you put extra bacteria that you've genetically modified into the patient's wound?

Evelina - Yes we do. And it works fantastic.

Chris - So the bacteria don't make the wound worse, they don't cause more inflammation? They're churning out this immune signal that they don't worsen the wound by being there?

Evelina - No. So what was seen in our experiments is that it is quite tough for them to produces this chemokine. It takes a lot of their energy so therefore they will not live for very long. And also we use a type of bacteria, their normal environment is not the wound, so they would also be killed by the wound environment. So we find them in the wounds for about one hour.

Chris - So they don't hang around for very long because that's sort of reassuring then. Although your putting bacteria in they do the right stuff and then they're gone?

Evelina - Yeah. And during this hour they produce enough of this chemokine to affect the immune cells.

Chris - When you then look at wounds that are treated this way, what is the difference in outcome between wounds that you do colonise, albeit temporarily with these microbes, and wounds that are just left alone?

Evelina - We see that we get a lot of granulation tissue,  which is the red healing tissue in the wounds at much earlier stages. We also see that we get the top part of the skin that cover the wounds fully at earlier stages. And then we also see reduce scarring and we have validated this in mice, mini pigs but also it also using skin biopsies.

Chris - One thing that's worrying me slightly is that you are putting these bacteria, which are genetically modified into a wound and they then could escape out into the environment, so is there not a risk? And I presume you've had to reassure various regulators that there is no danger or threat to the environment through the escape of these genetically modified bacteria, not just genetically modified, they are making human immune signals?

Evelina - This is something that we are following. We don't see that they have spread to the environment but this is something that we will continue to investigate and this is, as you say, we are obliged to do this by regulatory bodies. We have though done tons of risk assessments and we have also put them out in the parking lot and tried to find them and so on. But we also tested in - we took away all my water pipes in my bathroom because you can't just test on just new pipes - I mean that's not the real environment. Basically the worst-case scenario with the bacteria that we are using it was isolated actually from the rat intestine. We have other pilot data in the model of inflammatory bowel disease. So if they would spread to the environment they cannot really survive anywhere else than in rodent intestines, so if rodents would have problems with colitis, which is inflamed intestine, they would have a little bit less problem with that.

Chris - And how is your plumbing now?

Evelina - Well I got new pipes, but I was also very disturbed by how dirty my own pipes were!

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