By Adem Lewis / in , , , , , , , , , , /


Welcome to Invented Arizona.
I’m Paul Tumarkin and I’m Taylor Hudson. We’re with Tech Launch Arizona, the office of the University of Arizona that commercializes inventions stemming from research. Today we have the pleasure of talking with Dr. Julie Ledford, Assistant Professor of Medicine, in her office at the UA’s BIO5 Institute. And we’re also speaking with Dr. Monica Kraft, Chair of the Department of Medicine, who has it happens is traveling today so we’re lucky enough to catch her on the phone between her flights. Doctors Kraft and Ledford have spent their careers researching asthma and related diseases. Through that research they’ve
invented a series of peptides that have proven to be useful treatments. So Monica, tell us more about this research. Sure! So um before um Julie and I came to the University of Arizona I’d been studying asthma, really
mechanisms of inflammation and remodeling for many years and became
interested in how the airway, the asthmatic airway, handles infectious agents because patients with asthma have a lot of asthma attacks and that can lead to
hospitalization, loss of work in school, and extreme cases, even death. So the asthma exacerbation or the asthma attack is a real problem clinically for
patients. And so we wanted to understand better why the asthmatic airways didn’t handle infectious agents as well as the normal airway. And so perhaps became interested
in the innate immune pathways So thats the host response to insults. And in this, case we’ve urged infection but you could also think about irritants in the air pollutants as well as allergens potentially could also be in that
category. So in one of your recent studies you compared the levels of surfactant protein A, or SP-A, in lean or overweight asthmatics to those of obese asthmatics. Can you tell me a little bit more about those findings? We found that surfactant protein A, which is a protein that we all make in the lung,
and it’s really important in host defense, uh doesn’t work as well in asthma. We were actually able to extract it from the airway through a technique where we did bronchoscopy, where we can put a scope in the airway, which is a clinical test we do for patients with asthma, and actually
put salt water and take it out and actually extract the SP-A that way and look at how it functions. And so that made us wonder, why is it dysfunctional? Is it a genetic issue? Or is it a, you know, a post-translational issue? The advanced airway has a lot of reactive oxygen species, the very um obviously inflammatory milieu. So does that somehow break down the protein and effective function? And so we went ahead and sequenced the SP-A gene, which is actually made of two peptides, SP-A1 and SP-A2, and this one polymorphism at position 223 uh of SP-A2 fell out. And at that position there is uh a substitution of one amino acid, a glutamine, for a different one, a lysine. And that particular change occurs in about ten% of the population, as high as 30% in african-americans, which is important to us because uh the
prevalence of asthma is much higher in African-Americans. And then when we looked at clinical outcomes of asthma, we found that the patients who manifest with asthma had lower lung functions, they had worse asthma control by symptoms, and they had more in the way eosinophils in the airway. Okay so let’s stop for a minute and take a step back. What are eosinophils and how are they playing a role here? Eosinophils are a type of white cell that we associate with allergic inflammation. They’re present. They also can do damage to the tissue. And so with asthma there’s just too much of a good thing. We all have eosinophils but there’s too many of them in certain kinds of asthma. And so we think that the dysfunctional SP-A, in a sense, contributes to enhancing this inflammation, and therefore may be a mechanism by which patients with asthma
are more susceptible to infections. and then when they actually develop them, the SP-A doesn’t work as effectively to get rid of the pathogen. Julie all this research has culminated in the development of a series of peptides for treating asthma. Given what you know, will we be able to receive this treatment through an inhaler? I think we’re kind of
exploring that right now. We’re learning a lot about this process. Um we luckily have met with some wonderful pharmacists here at the University of Arizona that are kind of giving us options of dry powder inhaler versus co-suspensions and like really how to test, or formulate and test, our peptide in the best possible delivery mechanisms. So one of the important aspects of it is it needs to be delivered to the distal airway, which is where surfactant is made. So one of our challenges is getting something that’s really tiny all the way into the deeper part of the lungs. Wow okay that’s a hurdle, but given that
you’ve shown that it works, what kinds of opportunities do you see in applying this treatment to other lung related diseases? Definitely from the non-clinical aspect, I think what we see in lab would be applicable to many lung
diseases in that it can reduce mucin production, which is a problem in a lot of airways. And it looks so far in all of our tests it can
reduce airway bronchoconstriction, which would be really important for several different diseases. I just really want people to understand that this is a protein that you already have in your lung that does really great things, like it has so many wonderful applications in the lung. This is just a tiny piece of it that, potentially, asthmatics wouldn’t have in the functional state. So we’re giving back something that you normally would have in your lungs anyway, We’re just giving you back a functional form and it’s highly active and you’re going to get a high dose of this active piece. Well Julie Ledford and Monica Kraft,
from the office in the airport, thank you so much for taking the time to talk with us. And thanks to all of you for listening to Invented Arizona! For more information about this invention and all the other great inventions and inventors from the University of Arizona, visit Tech Launch Arizona on the web at techlaunch.arizona.edu We are @TechLaunchAZ on Twitter,
and you can also find us on Facebook and LinkedIn. And as always we invite you to subscribe to our monthly newsletter for stories, updates and events from around
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