Transcript
Dr. Neal Bhatia (12:00):
So let's play a little buzzword game for a second. So, we throw around words about the barrier. We think about barrier restoration, barrier integrity, barrier loss, right? I mean, we talk about all of those things with barrier, but where does barrier maintenance fit in? And it's tough, because we almost use them interchangeably and yet there is some nuance to each one.
Dr. Joshua Grosshandler (12:28):
No doubt. And I agree, and I think it gets really confusing because I think most of us are used to just interchangeably using a lot of these things. I guess how I, in my mind, frame it is I would take barrier maintenance almost from the outside. I think that that's what we're asking patients or parents of patients to help us with. That's more like the emollients, the gentle skincare, maybe even this proactive anti-inflammatory use from time to time with a medication.
But I kind of think of that as, OK, you get a little dry. We have this whole reaction with getting to, essentially, natural moisturizing factor being put back in to give a little bit more hydration. I think barrier restoration, to me, is really thinking about the keratinocyte, and thinking about what's happening within there. And I think that's where when we're talking about this pathway, I think it's able to do that, right? We're turning on these genes to really bring back what's happening inside that keratinocyte versus more the outside-in, if you will.
Dr. Neal Bhatia (13:31):
Yeah. No, and you brought up a good point before about atopics. I mean, they have an inherent defect in most of those proteins. Right?
Dr. Joshua Grosshandler (13:37):
Totally.
Dr. Neal Bhatia (13:38):
So, by bringing them back to some relevance, or stimulating their placement back where it needs to be in the epidermis probably brings that concept of barrier maintenance back to life. But that's where, again, I struggle with, okay, is there restoration of something that's already lost? So again, that goes back to I don't think we can use it to treat scars or striae or areas of atrophy, but I think we can maybe think about a component that's preventing the problem.
Dr. Joshua Grosshandler (14:09):
Yeah, and I agree. I mean, I think that, to your point, I don't think that the striae or some of these other atrophy-type-esque problems is really what we're talking about here. I think, but into maybe long-term, how are you changing a spot? Are we just treating acutely or are we using something that may give us a longer-term response? I think maybe turning some of these genes on may help us in doing that, amongst a few other potential pathways. And not to get maybe too far ahead of ourselves, but beyond just this barrier function, we do have the inflammatory side of things, too, right?
And one of the nice things that we were just mentioning is that, hey, this pathway actually controls both the Th2 side and the T helper 17 side. And how it's doing that is it's actually shutting down, if you will, that IL-4, that IL-5, the IL-13, the IL-31s. All the buzzwords that we're used to hearing with a lot of our biologic medicines that are part of atopic dermatitis and psoriasis, it's also shutting down IL-17, both A and F. And so we know that's also an important thing.
So I think it's multifaceted, but in terms of talking about fibroblasts, yes, aryl hydrocarbon receptors are on the fibroblasts. I'll be honest, I don't know enough about that side of things to really say, but it could be an interesting thing. Maybe Neal, you found the next iteration of something. You need to go down a dark rabbit hole, and we're going to cure striae with aryl hydrocarbon. But I think today in the way that we understand things, I agree with you. I don't know that it's really there.
Dr. Neal Bhatia (15:52):
Yeah. Of course, we're going to have everyone asking ChatGPT and everything else anyway, so we're pretty much on the outs looking in from that side.
Dr. Joshua Grosshandler (16:00):
Totally.
