If you recognise that sound, then you know real fear. That is a person with asthma in a desperate bid to take a breath that you and I just take for granted.
This is a QIMR Berghofer Medical Research Institute podcast.
Associate Professor Severine Navarro is an immunologist, head of Mucosal Immunology, and probably the most hopeful I have ever seen her. The backstory to this new protein that will change lives is just fantastic. Thanks, Severine, for joining us.
A/Professor Severine Navarro (00:38):
Thank you. My pleasure, Clare.
Clare Blake (00:40):
Severine, asthma is a huge deal?
A/Professor Severine Navarro (00:42):
It is a big deal. I would say that popular belief is it’s well managed, widespread, not such a dramatic condition to have, something that can be treated with a puffer and regular GP visits and on you go, no problem at all. But it really isn’t the case. There are multiple flareups. People will have a hard time controlling their disease, managing the disease. Often, it takes many years to work the regimen with the treatment. The reality is that the treatments available are just band-aids suppressing the symptoms as best they can, but it really doesn’t treat the disease. The disease is still there. It still progresses. It still damages the tissues, the airways, in the way that’s irreversible.
Overall, these patients experience a very poor quality of life. Sometimes it starts in early infancy, so you can imagine it’s a lifelong condition with miserable periods of time through the year, depending on the allergen triggers, whether it is due to pollens, rhythmed by pollen seasons, it can just start to be independent from allergen triggers altogether. And depending on the level of severity of the disease and the stage of the disease, it can be completely independent from that. Where temperature changes, cold temperatures, humidity changes in the atmosphere, and even exercise can trigger an asthma attack.
Clare Blake (02:13):
You think you’re managing it and then all of a sudden it changes.
A/Professor Severine Navarro (02:17):
Yeah, it evolves. And then, eventually, and that’s what we’re seeing now, is that people stop responding to treatment altogether. That means that the options for these people to manage their asthma is there’s basically none.
Clare Blake (02:29):
It’s quite traumatic to watch a child go through that.
A/Professor Severine Navarro (02:32):
It is. For the child as well, it’s absolutely anxiety triggering. It’s suffocating. It’s not the air not being able to come inside the lung, it’s the air not being able to be exhaled, so you suffocate in your own body trying to have a child calm down and rationalise saying help is on the way. It’s just nearly impossible. As a parent, that’s the worst thing that could ever happen.
Clare Blake (02:58):
Would we be surprised to know how common it is?
A/Professor Severine Navarro (03:01):
Just allergies in general, which comprise rhinitis, hay fever, skin allergy, which starts very early in life with eczema, and of course, allergy conjunctivitis and then asthma, food allergies as well. It’s the same group of diseases that affect different parts of the bodies, but they’re all linked and they can evolve starting with the skin allergy to hay fever, to then asthma. You can progress through all these symptoms through one lifetime, and it is a lot more widespread than we imagine.
Also in Australia, in particular, it’s rising. Now, we say one in 10 people are affected, but it’s higher in children. But we expect it’s going to be a lot more than that one in five in the next few years.
Clare Blake (03:47):
There are big challenges, like you said, with the treatments, the bronchodilators and the corticosteroids, kids having to carry them around, losing them.
A/Professor Severine Navarro (03:55):
It’s even worse when you start to imagine having to carry an EpiPen as well. Well, they’re expensive. Their expiry is very short, less than six months, and you have to renew them regularly, make sure you carry one everywhere. I think the terrible fear for parents in particular is that people actually don’t know how to use them. Usually, you need them in case of absolute emergency. You can imagine the panicky situation that you may find yourself, or imagine your kid may go through at school.
Clare Blake (04:23):
Hopefully, you could remove all that for everybody involved. This leads us to this amazing protein that you’ve isolated and produced, which looks like a game changer. Tell us about this extraordinary natural product behind it.
A/Professor Severine Navarro (04:37):
Right. The basic problems around allergy and asthma, and it’s also a common problem with autoimmune diseases, is that the immune system does not self-regulate, and it allows these inappropriate immune responses to expand and take over essentially. We call them inappropriate. It’s because immune regulation is missing. Our discovery is a protein from hookworms. It may sound a bit icky, but instead of using the worm itself, we’ve identified this molecule which we call anti-inflammatory protein-2, so AIP2. This molecule is quite phenomenal because it resets the immune system. In particular, it reeducates the immune regulatory component of the immune system and allows it to self-regulate the way it normally should have.
That’s why it’s a game-changer because it’s not a treatment for symptoms, it’s a treatment that reeducates the immune system, resets it normally. That means these diseases should attenuate in a natural way, and we’re hopeful that it may actually reset altogether. We say it’s disease-modifying because that means that the disease may disappear altogether. This is what we see in the lab, but we need to make sure that it happens in people. But if it doesn’t change the disease permanently, we know that it will have a benefit that will be long-term, and maybe even wean people off their bronchodilators and their corticosteroids.
Clare Blake (06:10):
What do you have in mind for the delivery?
A/Professor Severine Navarro (06:12):
So far in the lab, we know that it goes orally so that it could be a pill. Just taken through the mouth with a glass of water, so it dissolves later in the gut. From what we see in the lab, it’s a short-course treatment for a few months of relief.
Clare Blake (06:26):
I can see why you’re excited.
A/Professor Severine Navarro (06:28):
That would be amazing. Even little droplets for kids and on the go, they’re safe and protected. We have actually seen in the lab, and that’s why we’re so thrilled with this discovery, is that if it’s given early enough in young children, asthma doesn’t develop, allergy doesn’t develop. That means that if we took it as a preventative in case there’s a high family history of allergic diseases, or even just as a preventative approach in case allergy develops later in life, we can imagine just taking this as we take our vitamins when we’re young babies. Some people take probiotics. Well, we might be taking our AIP2 worm-derived treatments and make sure we are not going to get allergies.
Clare Blake (07:15):
This is amazing. Can we get back to the worm because it’s the greatest story. Hookworm infestations are bad. We don’t like them, but they gave you this great discovery. How did you find that?
A/Professor Severine Navarro (07:25):
When you’re a young child and your immune system is developing and it needs to be challenged by viruses and bacteria, so we say it’s good for kids to get sick at daycare even though it’s quite painful, but they need to have all this immune stimulation so the immune system can get educated. Worms were part of this environment that we should have been exposed to as young children, but because of hygiene and, of course, better common sense and medication, we’ve essentially eradicated worms from our environment. But now, we’re finding out that like other bugs, viruses, and bacteria, they were supposed to be present in the body to educate the immune system.
What we’re believing is that they were essential to educate the immunoregulatory component of the immune system. Because they’ve been eradicated, then these particular signals are weakened. That’s why we believe we’re seeing this dramatic rise in allergic and autoimmune diseases in developed countries.
Clare Blake (08:28):
The worm secretes a protein that does that for the system.
A/Professor Severine Navarro (08:32):
Yeah. Once the worm is infecting a host, it secretes lots of different compounds. Not just proteins, but lots of different things to manipulate the immune system and trick the host into not detecting it. Hookworms, unlike other worms, they’ve evolved to generate very wise molecules, because we know that hookworms, they remain within the hosts for a long time, and that is almost decades. To do this, they’ve developed these molecules that are very good at manipulating the immune system. That’s why we started questioning whether these hookworms had more benefit for human health. Instead of taking the worm, because some of these molecules of course might not feel very good in the body. We just went and selected the good ones and found luckily AIP2 that was very good at educating and regulating the immune system.
Clare Blake (09:29):
You mentioned the implications across other disease states, allergies and things like that, gluten intolerance. The extraordinary implications for this protein must be pretty exciting?
A/Professor Severine Navarro (09:40):
Yeah. I don’t want to sound like we’re just making this voodoo molecule applicable for everything, because it’s never one size fits all and it’s never so good to be true. But the reality is, what we’re seeing is any disease where its core activity is that it requires immune regulation and immune regulation is not happening properly, means that there’s a possibility for AIP2 to work. It may not be a cure, it may not be 100%, but that means that at least we won’t need immunosuppressants, like corticosteroids. We could just target immunoregulatory processes, promote them, and then hopefully get some reprieve, some alleviation of symptoms, and some improvement of the condition.
Clare Blake (10:29):
But there is a big problem at the moment. There’s a giant leap from where you are now from getting it to children and adults.
A/Professor Severine Navarro (10:37):
Well, I’m sure everybody must have wondered. When we were being taken through the wave of COVID-19 and urgently needed medication and vaccines, everybody was surprised that within a few months we were able to whip up a vaccine that definitely helped the population on a mass scale. The reason is the technology behind the COVID vaccine and mRNA vaccine existed for over 10 years, but it was just remaining in someone’s lab until we needed it urgently for mass intervention. All of a sudden, billions, not just hundreds of thousands, not millions, billions of dollars were put into this technology. And within a few months, it passed safety trials, and boom, it was on the market available for people.
Myself, like others, we have these technologies in labs that could really benefit populations, but we have to deal with small grant schemes, government grant schemes, and we’re competing against each other to get this funding. That means that we’re moving at snail pace to bring these technologies to the public. All it takes is this massive funding effort to say we need to treat this or we need to develop that and bring it to the market. So, the funding is the major holdback. I’m sure I’m not the only one saying this, but we cannot function and bring something to the public with small amounts. We need to do our due diligence and bring this technology to the public.
We’re so close, but we are still needing these due diligence experiments to be done before we can go to clinical trial. Unfortunately, it sounds awful, but we need a lot of money to get there because research is expensive. We need just a couple of years more of our research funding before we can get there. We just need help. We’re so enthusiastic with this technology. We just need help.
Clare Blake (12:36):
The savings would be extraordinary.
A/Professor Severine Navarro (12:39):
I believe so, yes.
Clare Blake (12:41):
Medicare and treatment. We’re talking about AIP2, anti-inflammatory protein-2. A-I-P-2 if you want to look it up. If you’d like to donate to this amazing research or find out about any of our research, go to qimrberghofer.edu.au. Thank you, Severine.
A/Professor Severine Navarro (13:01):
Thank you, Clare.