Therapeutic parasites

Humans have been playing host to parasites for generations, but in modern times our obsession with sterility means that we're living without many of these "old friends". So could there be a downside? Henry McSorley is from the University of Edinburgh explained to Chris Smith why an absence of parasites might be the cause of the increase of modern allergies...

Chris - With Rick is Henry McSorley who is also from the University of Edinburgh. It's fair to say that this sort of cat-and-mouse game between parasites and our immune system has been going on for generations. But in modern times, our obsession with sterility means that we're actually living without many of what we could regard as old friends. So, might there be a downside to this? What do you think, Henry?

Henry - Yeah, absolutely. The evidence for this comes from areas where parasitic infection is still very common. When we look at populations infected with parasites, they tend to have much lower levels of diseases such as allergic asthma, whereas in this country, as you were saying, improvements in hygiene and sanitation have resulted in our really eradicating parasites over the last kind of hundred years or so, and over that same time period, we suffered an epidemic of allergy. So, researchers are calling this the hygiene hypothesis, that we're too clean and this has led to us all being prone to hyperactive immune responses.

Chris - Henry, how could we disentangle the effects of a sterile lifestyle and an obsession with bleach and avoiding bugs like the plague alongside the absence of parasites because might it not be that the exposure to chemicals in our environment that we use to clean our environment are what are causing the allergy and it's nothing to do with the fact that we're now not parasite-laden because, as Mark Viney was saying earlier, actually parasites pretty much are harmful. They're stealing from us.

Henry - Well, that's true. I think all of this kind of correlative work, you know, correlation doesn't imply causation, really has to be tested. And that's really what we're trying to do by being able to control when the parasites infect. Looking at the development of allergy, we can show much more directly that parasites can prevent the development of allergy and maybe be exploited to create new medicines against allergy.

Chris - Indeed. How are people trying to do that?

Henry - Well, what we're doing is trying to move away from using actual parasitic infection. So, there are lots of clinical trials ongoing where people are being infected deliberately with live parasites to try and control diseases such as inflammatory bowel disease or allergic asthma. However, we don't know exactly how these parasites work and what they're actually doing. So, our approach to it is that we think it would be a much better idea to try and find the exact molecules that parasites are using to affect the immune system and the immune pathways that they're acting on. And then we could perhaps develop these parasite molecules as new medicines for these diseases.

Chris - So, you could swallow a pill rather than a worm which sounds a bit more "stomachable", doesn't it?

Henry - Yeah, absolutely.

Chris - Where are we on the way to doing that because it's pretty tricky to try and understand what that particular intestinal worm that is living hooked on the side of your intestine is doing to your immune system at the tiny level that these things are operating at isn't it?

Henry - Yeah, absolutely. So, the approach that we've taken is collecting all of the products that parasites release into the host and which we think contains some molecules which will modulate the host immune response. We collect these molecules and we find that by administering them, we can replicate many of these suppressive effects of the parasitic infection.

Chris - But is the site also important? Because if you have a parasite that has evolved to live latched onto your gut and deliver these things at the right sort of concentration at the right sort of level and in the right sort of way, it might not be just a simple case of, we'll copy those chemicals and then inject them or something. They might not work.

Henry - Absolutely and that's a really good point. And this is what we're finding. It may not be a single molecule. it may be a mixture and it very much actually depend on the dosing, yeah, exactly where you administer it. so, if you're looking at trying to affect colitis, maybe a pill would be a great idea. But if you're trying to affect asthma, then maybe something that you actually inhale straight into the lungs.

Chris - What sorts of disorders are you going for or what sorts of conditions do you think might be amenable to this sort of approach?

Henry - Really any disease where a hyperactive immune response causes problems. So, these are diseases such as allergy which I think is very common in this country, allergic asthma. But also, inflammatory bowel disease and also autoimmunity. There's clinical trials of infection going on in all of these diseases. But as I say, we're trying to create defined medicines to actually treat them.

Chris - And how far have you got?

Henry - We have got from the level of finding that we have whole parasite products, real mixture of stuff which can suppress things like asthma in mouse models. And we've, just in the last year actually, gone down to the level of having a couple of individual proteins which we can produce in a highly purified form in the lab, and these can replicate many of the suppressive effects of parasitic infection. So, these could be perhaps directly developed as drugs and in fact recently, just in the last month, we've shown that these molecules work directly on human cells in the lab in exactly the same way as they do in the mice. So, it seems that there's a very clear pipeline to make these into new medicines and put these into people.

Chris - Sounds wonderful. Congratulations! What about side effects or is there a downside to this?

Henry - Anytime you're talking about suppressing immune responses, there could obviously be side effects which would include increasing your susceptibility to infection or even to tumour surveillance so your immune system can stop you from having tumours progressing. However, what we're talking about in this sense especially in the asthma work is to try and tolerise people against inhaled allergens. These will be things like cat dander or pollen or whatever. So, you could administer these parasite products which are highly tolerogenic with your allergen that you want to tolerise against and hopefully, drive a tolerance state that would last for years and you could essentially cure allergic asthma.