Dr Sheila Donnelly – The therapeutic benefit of a parasitic worm

My name’s Sheila Donnelly, and I’m from the
School of Life Sciences, where we do a lot of biological research. For the purpose of today, given I’ve only
got five minutes, I’m going to crush about ten years of science on a very project that
I work on, into hopefully five minutes. I was going to start with quite a sneaky request
for a standing ovation, and I would create this by asking everyone in the room to stand
up if they could answer yes to the following question: do you know or do you yourself suffer
from diabetes, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, cirrhosis
and so on. If anyone in this room knows of someone or
themselves suffer from these diseases, you have an immune-mediated disease, and there’s
quite a few of us in the country. This is a disease where your immune response,
which has evolved to protect you from infection from bacteria and viruses, is now turning
on your own body. So for example, type 1 diabetes – the immune
response destroys the insulin-producing islet cells. In MS, the immune response is destroying the
insulation around the nerve cells which is necessary for communication. We recognise it’s probably an endemic of these
immune-mediated diseases. There’s millions of people around the world
afflicted by them, and we need to know why. We don’t have a cure for these diseases, nor
do we really have an effective treatment. But we need to understand why these occur
in order to develop an effective treatment – and this is where my work comes in. Typically people consider these diseases as
having a genetic basis, but the rate at which they’re occurring and increasing over time
is too fast for these diseases for these to be genetically based, or certainly solely
genetically based. Instead, we think there’s an environmental
factor involved. So either something has come into the environment
in the developed world, where these diseases are found, or an environmental factor is removed. I will say that this is now where I’m a bit
biased. I’m a parasitologist, but I believe that the
environmental factor that’s been removed is parasitic worms. If you look at these maps on the right-hand-side,
we have the instance of diabetes, type one, and on the left-hand-side, a map where parasitic
worms are found endemically – that is, permanently found within populations in society. And there’s a really nice clear inverse relationship. So the question is – by removing parasitic
worms, are we making ourselves susceptible to disease? And how could this possibly be the case? These worms are pathogens, infectious organisms. Yes, they are, but they’ve been around for
a very long time. So we evolved in the presence of these parasitic
worms, our immune response was educated in the presence of these parasitic worms. So what if I was to tell you that these parasitic
worms are in fact part of the immune system? Perhaps by removing them, we’re dis-regulating
or unbalancing the immune system. By taking them out, we’re getting auto-immune
disease. If we put them back in, do we balance the
immune response? It may sound crazy, but this gastroenterologist,
Joel Weinstock on the right-hand-side, tried it. He thought the epidemiological evidence was
so compelling that there was definitely truth to this possibility. He took 29 patients that had ulcerative colitis,
infected them with the pig whipworm, and he found that most of them went into remission,
and remained in remissions four to six years later. The caveat? It was a very small clinical trial, and not
blinded, no placebos and so on. But the data…everybody went crazy, this
is fantastic, the first proof of concept that worms may actually provide therapeutic relief
from disease. So we now have a number of human trials currently
ongoing around the world for MS and cirrhosis and some for asthma, in fact. We’re awaiting the outcomes of those to see
how much truth there is to this hypothesis. So there’s evidence that it’s good, and it’s
certainly very encouraging, but there’s a downside, and these pictures on the left will
show you. So the parasitic worms, they need a mammalian
host. If we want to use this as a therapeutic, we
need to grow them in a mammalian host, and collect them in one way. You can see the picture of the pig, where
the arrow’s pointing, and you can see the picture of the human host, where the arrow’s
pointing. We collect these from faeces. So obviously there’s a risk, it’s not really
going to be a global therapeutic. And again, they are pathogens, so there is
physiological outcomes to having a parasitic worm, so not an ideal solution. So instead, at UTS, we’re taking a different
approach, and this slide summarises my entire life work. On the right-hand-side, we have the parasitic
worm that I work with, and you can see this beautiful branch structure throughout its
body, and that’s the gut, its stomach. It’s filled with haemoglobin and lots of other
molecules, which the parasite secretes in order for it to migrate around the host, to
feed, to produce eggs and so on. So we extract the contents of those gut in
flasks in the lab, and if we move along, you can see all my years in one picture. We can isolate what that worm secretes, identify
them, work out what they are, then synthesise them in the lab as individual molecules, and
then use animal models of disease to see if those individual molecules can provide therapeutic
effect. And I’ve summarised our most recent and very
exciting data on the left side, where we have a mouse model of multiple sclerosis. And the black line, which goes in waves, is
the control mice, and the flat green line are those mice that were treated with a single
parasite peptide only three times. So it’s very encouraging, we’re currently
trying to commercialise, so very interesting to look at our rail at UTS to see where we
can progress. And I would finally just like to acknowledge,
as a science project, it has gone on for a long time with a lot of students and researchers
involved. So thank you, and thank you for your time.

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