Magnetic Nanoparticles: The Future of Hearing Loss Treatment? Exploring the Latest Research with Dr. Daniel Sun

Well, welcome to This Week in Hearing. It’s going to be a very interesting conversation today. You know, the hearing healthcare space just continues to evolve in a number of different ways. That’s very, very exciting. And today is no exception, as I’m joined by Dr. Daniel Sun He’s an associate professor in the division of neurology and neurotology and skull based surgery at the University of Cincinnati. And some of the research that he’s doing as it relates to service delivery strategies of the inner ear using magnetic field to treat hearing loss is very, very fascinating. So, first and foremost thank you very much for joining us. And as we get started here, if you wouldn’t mind introducing yourself and then talking a little bit about what inspired your work. Sure, yeah. Thank you. Happy to be here and thanks for inviting me. So I currently serve as the associate professor of otolaryngology and division director of neurotology at University of Cincinnati. And prior to joining UC, I served for a number of years on faculty at Johns Hopkins University School of medicine. And so it’s great to be here. Our work is really focused on how to get medications better into the inner ear or the cochlea to treat hearing loss. Were really inspired by the challenge right now, which is twofold. First there’s really very few medications that can actually treat hearing loss. Really the only medication we have today is steroids, and steroids don’t even work very well. And the second challenge is that there are actually a whole series of pretty exciting medications that could be coming down the pipeline. But the problem is there’s not a really good way to get those medications into the inner ear, into the cochlea, where sensorineural hearing loss occurs. The reason for that is that these medications are what are called biologics meaning that they’re not small molecules like steroids. They’re much larger molecules. They could be proteins, they could be nucleic acids like DNA that’s used for gene therapy. And it’s very hard for these larger medications to cross through into the inner ear where hearing losses happening. Yeah. So just for those of us who may not be familiar, are these are these medications taken orally? I would assume that some of these are going to be entered into the ear through some sort of trans-tympanic mechanism. Can you explain a little bit about that, please? Yeah, that’s a great question. You know, when we think about how to give ourselves medications, there are some ways that we can do that. One is we take by mouth and it gets absorbed in our gut and goes to where it needs to go. We do that with steroids. But it turns out that not all the medications get to where they need to go, and it gives us a lot of side effects like when we take high dose steroids. So instead, one way we deliver drugs in the ear is by directly injecting it behind the eardrum, called a intra-tympanic injection which many of your listeners may have heard of already. That in itself is actually fairly minimally invasive. It’s something that we do every day in clinic with a drop of numbing medicine on the eardrum. But it turns out that this technique, while it’s minimally invasive and easy to do, doesn’t work so well in terms of actually getting medications into the inner ear. And we expect that for the larger medications, like proteins, it probably won’t work at all. The reason for that is that the medications that we put behind the eardrum needs to cross a very small but complex membrane called the round window membrane that separates the middle ear from the cochlea. We actually don’t have a very good understanding of what gets across the round window membrane by how much something gets across and how these newer medications can actually do that if they’re so large. Yeah, so that’s interesting. So we have these medications, there’s a, for lack of a better term there’s a waste of these medications, depending on how you take them. So you have a new methodology and you don’t know how they go in. And so you came up with a novel way of, for lack of a better term kind of following where these things go. And that’s using magnetic resonance, is that correct? Well, so a lot of people have tried to find safer, more effective ways to get these medications into the inner ear. One thing that we have looked at are nanoparticles. The advantage of nanoparticles potentially are number one, that they are already FDA approved in this case. For other indications in the body. For instance, magnetic nanoparticles are already used for imaging or for other treatments. It’s just that they’ve never been very systematically investigated as to whether they could also serve as drug delivery vehicles in the ear. Our work has found that in fact they can, but they need to be designed and engineered in very specific ways in order to have a shot of achieving this purpose. The other advantage for magnetic nanoparticles, theoretically, is that because each of them contains a magnetic core, they could actually be theoretically driven or steered by a magnetic field into the inner ear, across the round window membrane. And so what inspired you to go down this road? I mean, this is really fascinating. What inspired you to go down this road? How did you get there? So you know, my background is in chemical engineering, so I’ve always been interested in drug delivery technologies. And one thing that I was really enjoying in my career is working with engineers and basic scientists to bridge the gap between the discoveries that we make in the lab and what’s needed to actually apply them at the bedside. So at both Johns Hopkins and University of Cincinnati, I’ve been privileged to be immersed in these environments where I we can work side by side with engineers and other scientists to sort of come up with these creative strategies and solutions. And one particular inspiration for our team is that magnetic nanoparticles their sort of proof of principle has been demonstrated by my predecessors in the field. But we really lack understanding in terms of how to build this rocket so that it can actually get us to where we need to go. The design specifications so to speak and then their magnetic properties also has a lot of potential for further biomedical research because no one’s really looked at you know, exactly what kind of magnetic field is needed. You know, how would we make that field work in humans? And, you know, other ways of acting active, activating them, such as with clinical lasers, for instance, which is something else that we’re currently looking at. So all those things, you know, I think not only represent really interesting research questions, but also, you know. Potential advancement for the clinical treatment of hearing loss. If we could find a safer, more effective way to get these medications into the inner ear. In terms of some of the findings themselves, I think one finding that surprised us was just how much the size of the nanoparticles matter. We’ve had a long term understanding in the field that how much a medication gets across the round window membrane is really dependent on size. You can imagine smaller medications can get through easier, larger medications have a much harder time amongst other properties. But when it comes to magnetic nanoparticles, because of the complexity of their chemistry and physics and adding on the magnetic field interactions on top of it, we find that actually tens of nanometers make a huge difference in terms of how well a particle performs in terms of penetrating the round window membrane. For instance, in recent publication we found that particles that are between 60, 70 nm tends to be in the sweet spot and even particles that are 80 or 90 nm tended to have a much lower penetration. That’s interesting. So the drugs that you’re using are FDA approved. The methodology that you’re using is somewhat novel and so are there clinical trials that have to take place. What’s the next step in order to move this from the laboratory and transition it into a clinical setting? So the medications are actually not FDA approved. Yeah because they are still in the pipeline stages. Some of these medications are actually endogenous to our ear anyways. For instance neuronal based growth factors that can help keep the neurons in the cochlea healthy. And what inspires our work is really wanting to not just say, hey, for medication A, let’s build a delivery vehicle for medication B, let’s find a different strategy. We think what can really make an impact is building a common rocket that can get us to many different places in orbit, whether it’s for neuronal based growth factor or nucleic acids DNA gene therapy, for instance. And that was why we started developing magnetic nanoparticles, because all these nanoparticles share common properties where they all have a magnetic and their coatings can all be chemically modified as needed to, you know. Theoretically carry any number of medications, regardless of what they are and regardless of what state of development they’re in. So it looks like there’s a timeline that’s associated with this. Can you share that a little bit? Is it a couple of years or are we looking several decades out? Yeah, it’s always hard to predict these things. Regulatory approval is a whole beast in itself. But we’re certainly very much in the early phase, preclinical stages, where we’re trying to work on this systematically and rigorously to first make sure that we have a grassroots level understanding of the different scientific aspects of its safety and biocompatibility in the ear. And then hopefully we can look at this in actual human tissue also, as I mentioned before. And then we will be thinking about potential clinical trials. Yes. And that’s interesting. So you would have a physician that would be the administrator of this aspect, and then you would have some sort of an intervention and potentially a treatment, which is where I would assume the audiology might fit in. The audiologist might fit in. What would that look like? I know it’s early, but what might that look like? If you have any impressions? Yeah, I think, you know, in terms of the magnetic nanoparticles the you know, we’re really looking at, you know, intra tympanic injections that can be applied to, you know, some of the exciting potential medications that’s coming down the line in terms of you know, our overall understanding of hearing loss and the treatments for hearing loss. I think that’s where there can be a lot of roles for audiologists who are very much on the front lines of caring for patients with hearing loss. And I think that’s probably where some of our other current work is much more applicable and relevant. Yeah. Before we got on, we were talking a little bit about this other work. Let’s shift gears a little bit since the audience, that’s the majority of the folks that listen in are clinicians that’s a little bit different. Can you now describe as we shift gears into what that new work might look like and what it is? Yeah. So whereas before we were talking about very much animal based, bench top discovery type of engineering work are the other arm of our research program is really much more focused on present day patient care and clinical improvement. And we are actually very excited about two particular efforts there and they both revolve around how to better care for patients with hearing loss. The first one revolves around actually using a cutting edge MRI technique to understand how the connectivity in our brain may change based on someone’s hearing loss and how long they’ve had that hearing loss. And the second one revolves around how best to help patients who may have received a cochlear implant, but for whatever reason, may not be doing as well as they like with that cochlear implant, which I know is also. I think both of those situations are scenarios that clinicians, especially audiologists, come in contact with on a daily basis. Yeah, that’s really, really interesting. Let’s go to this first part here, which is the non-cochlear part. So you have this imaging that goes on, and the idea here, is it to preserve hearing loss, or is it to restore hearing loss, or is that something you’re still trying to determine, or is it both? Yeah. So what really inspired this work is really a question revolved around, let’s say that we have someone who was born with normal hearing, and then 30 years ago, for whatever reason, lost hearing in one ear. And this is a situation we face pretty frequently in clinic. They come into clinic and they’re very much wanting better hearing in their ear that’s been deafened for 30 years. You know, maybe it’s one year that’s been definite, maybe it’s both years. But as clinicians, we have a really big dilemma here because we don’t know whether a cochlear implant can truly work or not. Right, right. You know, oftentimes we think cochlear implants don’t work when someone has been deafened for more than ten years, let’s say. But we also know that there are patients who may be deafened for over ten years, let’s say 15 years, and they get a cochlear implant, and against all expectation, they can hear with that device, and they do really well with it. This is a dilemma that I think, as clinicians, we struggle a lot with how to counsel those patients and whether to counsel them to try a cochlear implant or not. It’s something that patients themselves struggle a lot with, whether to go forward with a procedure not knowing. Whether the procedure would truly help, but not having any other options, so to speak. So what we’ve done is we partnered with bioengineering at UC, actually. And brain imaging happens to be one of the strengths here. And the institution happens to have one of the most advanced MRI scanners probably in the country. And we are looking, and we actually recently just received a grant to look at using this type of MRI to better understand how someone’s auditory circuits may change based on how long they’ve had their hearing loss. And the idea is, first let’s understand whether our brain changes or not based on the severity and duration of our hearing loss, and then let’s apply that knowledge to see if we can better predict whether someone who’s had that long term hearing loss could potentially benefit from a cochlear implant or not. So, if I’m understanding this correctly, it’s almost a predictive measure of auditory plasticity. Yeah, that’s a great point, and I think that’s probably a really good way to summarize it. We always hear about how important neuroplasticity is for our hearing, for auditory learning, and eventually for how well someone does with a cochlear implant. But there’s actually very few, or if any, biomarkers or imaging biomarkers of what neuroplasticity actually is. So that’s something that I think really inspired our team in terms of trying to figure out a more personalized medicine approach to this group of clinical patients that really struggle with their hearing and how best to help with that hearing, by understanding really what’s going on, whether there are any changes at the brain level that could give us clues as to how better to help these patients. Yeah. What’s going through my mind here Daniel, is the fact that if once you get the results from the imaging and you’re a clinician, you now have a roadmap, so to speak, for treatment. But as you and I were talking earlier, audiologists in at least Maryland now have the abilities to order imaging. And so how do you see this new frontier of audiology in the expansion of its scope play into this, while we already know the backside of the story? Yeah. I’m definitely not an expert in the legislation. That was just passed. I don’t know the details, but I think a lot of questions have yet to be answered in terms of the nuts and bolts, in terms of how something like that would be carried out in day to day practice insurance authorizations, which, unfortunately, is what drives a lot of our healthcare system nowadays, you know. So I think the jury’s still probably out on how that will look in. In real life. But you know, I think making imaging a better tool for understanding our patients hearing loss and helping our patients with hearing loss you know, is what would be a benefit to. To everyone, patients, you know, physicians, audiologists, you know, the world. Yeah, no, absolutely. I think it’s going to be very much, at least on the cochlear implant side very much a continued team approach where everybody will come together and do what’s in the best interest of that patient. So I appreciate that comment. The other comment that you made was about software, if I remember right, that there’s some software being developed. Can you talk a little bit about that, please? Yeah. So we’re pretty privileged to work with a collaborator in bioengineering here at UC, professor Tom Talavage who is the chair of biomedical engineering and who is really a world expert in cochlear implant programming. His lab has actually developed some novel programming strategies sort of like new software for our smartphone, let’s say, that may make that device work a little bit better in terms of making calls. And so we’ve been really excited to try this software in some cochlear implant patients. I think the exciting part is that this is not something that patients need to have a new device for. This software just piggybacks on the hardware that they already have to try to deliver the signals in a way that can help patients hear better. The primary results have been very encouraging, and we’re actually expanding our enrollment to test this in a larger set of patients. Yeah, and if you’ll share that information, we can post it on the. On the with this video here. And hopefully that will then allow for some additional marketing that will then allow folks that are interested to contact you and you know subscribe to being a participant in your study should you need those folks. So we’ll certainly, certainly help you out with that. The last question that I have, and this has been a really, really fascinating conversation, is, is there a repository, is there a place on your website or somewhere where we as clinicians can go to maybe get some additional information and watch the evolution of the things that you’re doing so that we can stay abreast. And as they become closer to being implemented in the clinic one, we can develop the tools that we need, we can train appropriately, and then three, we have a better sense of what gains the average patient may get that they’re not getting today. Yeah, I think that’s a great idea. And I think that’s probably where my lack of IT skills become evident. But yeah, I think the hearing space, as you mentioned, is you know, tremendously exciting and tremendously hopeful. I think we’re in an era of great hope and optimism with the recent results from the congenital genetic gene therapy trials in kids to better and better drug delivery technologies to cutting edge imaging modalities for our patients. So I think there’s a lot to look forward to and I’m privileged to work with a great team to be a part of that. Well, and we’re very fortunate to have someone like you and there are others that are doing this kind of research that’s helping to push audiology in the direction it needs to move to better serve patients. Hearing aid has been around for a number of years and it’s certainly a solution, but for other folks, there may be other alternative solutions that may be better. And I don’t think that we’ve really even touched the iceberg of that yet. So thank you for the work that you do and that your team does, and you know, we’ll certainly be on the lookout for your successes and hopefully have you back on the show here sometime down the road and say, hey, you were here in you know, in August of 2024, and now you’re here. Man, that’s a heck of a bunch of growth. And now what’s next? Yeah thanks so much for having me. And, yeah, thanks for all you do also, and disseminating the sort of advancements and news in the field to your listeners so that they’re aware of what may be coming down the pipeline. Well, it’s our pleasure. And thanks for thanks for being on, and we’ll certainly be in touch down the road. Yeah, thank you.