Justine Tigno-Aranjuez, Assistant Professor of Medicine at the Burnett School of Biomedical Science at the University of Central Florida, talks about possibly discovering a new way to treat allergies.
Interview conducted by Ivanhoe Broadcast News in 2023.
What happens in the body when someone suffers from allergies and specifically allergic asthma?
Tigno-Aranjuez: Yes. So when we are exposed to allergens, we mount a specific immune response. It’s called the Type 2 response, and in the airway that begins with the airway coming into contact with the allergen. And then that tends to produce a bunch of mediators that tell your adaptive immune system to produce these, it’s called a Type 2 response or Th2 response, and that produces the cytokines IL 4, 5, and 13 that are responsible for a lot of the symptoms that we associate with asthma. For example, the mucus overproduction, the constriction that happens, and then eventually the airway remodeling. If you’ve ever been tested for allergies, usually they either do skin prick tests or they’ll take a little bit of your blood and look for IgE, and that’s another thing that happens that is associated with this Th2 response.
What was the traditional way to treat allergies?
Tigno-Aranjuez: So because people already understand what happens in this allergic cascade. They know you’re producing these cytokines IL 4, 5, and 13, and as well as IgE types of antibodies. Those are the things that have been targeted a lot. So they either target those cytokines or the receptors for those cytokines or they target IgE. And so for example, if you’ve heard of a melisma that’s directed against IgE and that’s biologic that has moved into the clinic and has been used now by patients. So that’s been the more traditional approach to target these downstream mediators. And what that does is suppress a lot of the symptoms associated with allergic asthma.
Who would benefit the most from this research?
Tigno-Aranjuez: So anyone suffering from allergies or asthma. Because what we found is, we found a novel receptor for house dust mite. So house dust mite is one of the most common allergens. Even if you don’t think you’re an allergic type person, maybe if you test yourself, you might actually be allergic to dust mites and not be realizing it. So one of the most common aeroallergens that’s out there. So we’ve discovered this new receptor that can bind to this allergen, and we think we know how it works, at least in a specific type of cell. So if we understand more about how it’s function, then potentially we could target it and because it’s interfering with a process that’s very early, like the first time this type of cell, a dendritic cell sees the allergen recognition. And we have the potential to potentially modify the disease course or there’s a potential for it to have a greater effect than just trying to basically suppress the symptoms.
Can you explain the science of stopping the allergic reaction before it happens?
Tigno-Aranjuez: Yeah. So in a typical allergic reaction, so I alluded to the allergic cascade that happens, your heptune gets activated, secretes a mediators that activates other cells like the dendritic cells which help lead to this Th2 adaptive immune response that leads to the IL4, IL5, and 13 production leading to the symptoms of allergy. So the part that we’re trying to interfere with is not the downstream part where everything is already being made, like IL4 and 5, IL13 are already being secreted, IgE’s already being secreted. But instead we’re trying to interfere pretty early. So basically at the stage at which cells are recognizing allergen. So we think that if we interfere at that point and potentially in cells that are really important very early in this cascade, then you could prevent all the rest from happening. If you can interfere with the recognition, then potentially you could also prevent all the cascade from happening.
How has this new research shaped the medical field or how do you think it will improve the medical field research?
Tigno-Aranjuez: Yeah, so because it’s something that has never been described before, so people hadn’t been looking at this receptor. If we understand completely how it works, that it could be a potential target where we could manipulated to get the response that we want. So in the case of IL-1, if it seems to be down regulating the response. In the case of allergy that’s good, because we want less of the inflammation. So if we could say activated in some way or maybe increase the levels of this receptor in a particular cell type, that might be potentially beneficial. But this is future future steps. Right now we’re really trying to understand the biology.
Is there anything else that you would like to add about this new research?
Tigno-Aranjuez: Yes, so currently a lot of the what we call like biologics that are being developed to treat allergic disease. Like I mentioned earlier, they’re really targeted against these mediators that are produced once the allergic cascade is already underway. So basically, if you think about, you have flooding in your basement, what you’re trying to do, what the approach has been, a lot of the times it’s just to basically be getting a bucket and like throwing out the water. Getting the water out. We want to basically fix the leak earlier on so that it doesn’t become a flood in your basement. So that’s what we’re looking to see, to be able to intervene somewhere earlier. And the earlier you intervene in the response, it looks like you have a greater chance of potentially changing the response. So I mentioned earlier, Type 2 response or Th2 response that’s associated with allergy. But may be if you intervene earlier, maybe you could deviate that response. You could move it to a Type 1 response or maybe a regulatory response. So that you’re not producing this response that is associated with allergen or allergic asthma. And the second thing is, what people have been seeing, is that again, the earlier in this cascade that they intervene, the more efficacious the treatment seems to be. There’s this one drug that is currently being used now, it’s called tezepelumab and it’s basically blocks one of these early mediators that are produced after your airway, epithelium comes into contact with the allergen. And that actually has been shown to be very efficacious for a number of asthmatics. And the nice thing is that you don’t have to be a specific type of asthmatics, some of the other biologics, you have to have a certain level of IgE or certain level of sinophilia and then they can put you on this particular treatment. For spell map which works really early, again, there’s not that much restriction on who can use it and it seems to be more effective. So we’re hoping to do the same thing by finding a target that’s very early in the cascade. If we can show that we can change the response early on, that everything else downstream will be prevented.
I just wanted to know, what would it translate to; is it going to be, like, asthma form or is it just something you just take to like that response?
Tigno-Aranjuez: Oh, sorry. So right now we haven’t really test it, manipulating this particular receptor for therapy. But potentially, if you could somehow increase the levels of this, that would lead to downregulation of the response. So what would that look like in terms of a therapy, it’s not so straightforward, unfortunately, as taking a pill a little bit more invasive. It might need to be some retroviral therapy where you get your body to be expressing higher levels of this in a particular cell type. That’s one potential way. Another way is, you could also potentially use antibodies which just activate this receptor. So without the des mite, activate it and you basically downregulate the response, then that might also be beneficial. So currently, we don’t have an exact answer to how this would potentially be used in the therapy, but that’s something we’re very interested in testing out.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Christin Senior
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
