This week, Dave Kemp takes a closer look at how innovations in genetic screening technology are having a clinical impact to preserve the hearing of at-risk infants. He is joined by Dr. John McDermott, Dr. Nicola Booth and Dr. Gino Miele, to discuss how Genedrive’s genetic testing device is allowing clinicians to determine whether a child is at increased risk of permanent hearing loss from aminoglycoside use due to a genetic variant.
This type of analysis has traditionally taken days, or even weeks to obtain, can now be done in under an hour on-site.
The Genedrive test is rapid, portable, and cost-effective, making it an attractive option for hospitals and clinics. With this technology, doctors can quickly identify at-risk babies and take action to prevent hearing loss.
- Full JAMA study link here
- Details on Genedrive device here
Full Episode Transcript
All right, everybody, and welcome to another episode of This Week in Hearing. I am absolutely thrilled to be joined today by team of three great individuals. I have Dr. John McDermott, I have Dr. Nicola Booth and I have Dr. Gino Miele. So thank you three so much for coming on the show. Today we are going to be discussing genetic screenings in the world of hearing healthcare. I think kind of the forefront of maybe how a lot of our screenings and that part of the process is being innovated upon. So, on that note, let’s kick it over to the guests, let them all introduce themselves. We’ll start with you, Nikki. Ladies first. Thank you. My name is Nikki Booth and I am the research nurse manager at the neonatal unit at St. Mary’s hospital in Manchester. Fantastic. John. Thanks very much. I’m John McDermott. I’m a clinical geneticist based here in Manchester and a research fellow at the university. Fantastic. And Gino hi, I’m R&D director for a company called Genedrive, based in Manchester, in the UK, and we’re focused on development of molecular invitro, diagnostics and medical devices. Fantastic. Again, thank you three so much for joining today. So let’s start with you, John, because I know that you and Professor Bill Newman were sort of at the tip of the spear here in developing this study. So why don’t you kind of lay out what the study was and is and how it came to be? Yeah, sure. So, our group are particularly interested in a concept called pharmacogenetics, which is how you can use genetic information to improve the safety or effectiveness of medicines. And we know that many medicines. Genetic changes that are common in the population can impact how they work in different people. And there’s been robust evidence built up over many, many years around individual gene drug pairs. And one of those is the relationship between a gene called rnr1 which is a mitochondrial gene, and aminoglycoside antibiotics. And in the latter part of the 20th century, a number of publications came out. Noting that certain individuals in certain families were predisposed to aminoglycoside induced otototoxicity, so aminoglycoside induced hearing loss when they received just a single dose of aminoglycoside. So a profound and irreversible reaction. And lots of studies were done describing that relationship. And it was in 1993, a paper came out showing that it was related to a single change in this gene position 1555, an a to g substitution. That profound relationship between a single gene change and aminoglycoside induced hearing loss has been established for nearly 30 years now. But the question was, how can you actually use that information in practice to improve patient outcomes? And a lot of that is about developing testing strategies and doing implementation trials. And so the standard genetic testing usually takes many weeks or many months to do a test. So on the NHS, there is a test where you can look for this gene change, but it takes around three to five weeks to get a result back. So I see patients in my clinic who might have hearing loss and when we’re investigating the cause, I can request that test. And that’s fine, because works in that paradigm where you have a patient and there’s no clinical urgency, but we know, and Nikki will be able to talk a lot about this, that there are another cohort Of patients who receive large doses of aminoglycosides, and that’s in neonatal sepsis. So babies coming through the neonatal intensive care unit around the world, and specifically in the UK, from our perspective, the guidance is that they should receive an aminoglycoside antibiotic and a beta lactam, so, like a penicillin based antibiotic, and those individuals should receive that antibiotic within an hour. And so that was the challenge that we were faced with, simply with the technology that existed. You couldn’t do this test in clinical practice for that cohort of individuals. And this was a clinically significant problem. At scale, there’s around 100,000 admissions to NICU each year and who receive these antibiotics. So based on the population prevalence of this change, which is around one in 500, it’s around 200 babies who are at risk of hearing loss. So that was the kind of clinic. Challenge we were faced with. And around five years ago, we partnered with Geno’s company with Genedrive, look and see whether we could develop a test that could deliver a clinically relevant result in a clinically relevant time frame. So that’s really the background. I love that. Thank you so much for giving me some background there. And just to kind of summarize, rise, as I understand it, so you said there is a way in which you could detect this genetic anomaly, if you will, but with the existing standard in the NHS, it takes three to five weeks. But as you’re saying, of the 100,000 babies that would be born every year that are in the neonatal, that would potentially need this medication, that you need to administer that medication within an hour. And so the challenge is that that medication can actually be quite damaging from a hearing loss standpoint if you have this. Genetic anomaly. And so you have to be able to screen that under an hour. Right. And so then enter Gino and genedrive. So, Gino, I’m going to kick it over to you now. Can you walk me through what the challenges were with this and maybe just kind of a high level overview of genetic sequencing, testing, the innovation that’s occurred that has allowed for the kind of breakthrough to, in John’s words, make is clinically feasible and relevant within the time constraints and all that? Yeah, sure. So, as John alluded to, it was about five years ago. Like all or most great science sort of occurred over a bit of a coffee at a conference, to be honest. John and Bill had a clinical problem and we had an instrument which was capable of amplifying DNA in rapid time frame. So at that point, it was about an hour. We discussed the possibility. I got some grants for pilot studies. At that point, the instrument was a bit different than it is just now. It was mostly positioned for resource limited settings. So portability was key, simplicity was key, but speed was key. But the challenges with this were the result had to be very clear, very easily actionable available to the clinician in under an hour, but ideally under half an hour. So to be able to bring a complex genetic test to point care to be used by users which have no real prior experience of implementing genetic tests into emergency care, required a couple of things to happen. One was we ought to develop our test, which the chemistry was able to do that within half an hour. And there were some challenges around that with. And in the lab it’s fine, but bringing it to the point where it’s usable in a sort of emergency care set and has numerous challenges associated with it. So we have to develop what’s called a freeze dried assay for this so that everything’s ambient stable, stable at room temperature, which is really important when you think about the logistics. We’re trying to avoid the logistics of cold chain storage, storage and fridges and freezers around the world in all of the settings. So everything’s ambient stable. And we utilize a technology called Lamp, which is capable of amplifying DNA very quickly to very large amounts. And we repurposed that for inclusion in our reader, which is an amplification device. So it amplifies the DNA in, does the complex genetic analysis for this single variant and then very importantly, just returns a clear result. So no user interpretation required. Just variant detected or variant not detected, and then the healthcare workers can act on the clinical guidelines in that country. At that time, I think that was technical challenges. They’re fairly easy to overcome. But coming back to this whole notion of complex genetic test is usually done in a central lab, as John said, three to five weeks. And what you’re trying to do here is put it into the hands of the people who are at the point of care and need to make those decisions. And that was a bit of a learning curve for us to bring that into. It was a learning curve and a huge opportunity as well, to be honest. But it allowed us to under the implementation study, learn what Nikki, Nikki’s team, and representative users, needed from this instrument and this test in order to be able to concentrate on the clinical care rather than the technical aspects of setting up a test. So there was a couple. Things there that were extremely useful for us to learn. And we transitioned from the type of instrument we had before into what we have now, which is we’re commercializing a true point of care device that can be used at point of care and importantly has features that make it amenable to ease of use in those settings as well as the ambient stable reagents as well. That’s where we’re at. Yeah, this whole thing is so fascinating to me. I mean, it seems truly cutting edge that you can do something like sequence somebody’s genetic code in a matter of under an hour. It just seems like this is going to lead to so many different kinds of breakthroughs as we understand more on an individual basis, what people are susceptible to and all that. So Nikki, over to you here. As somebody that’s actually been using this. specific Genedrive machine and administering these types of screenings. Can you talk about what your experience has been like using this? Yeah. So when we first started the study, I guess the first challenge was in terms of training a fairly large workforce of nurses, because obviously babies are born and admitted and any time of the day in UK standards, our unit is pretty big. We did have over 250 members of the nursing team, and it will be the nursing team that would take the swab and process the test and we have maybe about 100 babies per month admitted onto the unit. So we had to think about training staff and how that would work. And we obviously had to consider the fact that. When a sick baby is born and admitted to the neonatal unit, it is obviously a really busy time anyway. And the priority is absolutely stabilization of the baby and the golden hour, that 1 hour that we concentrate has known impact on long term outcomes, which is why we have that goal to stabilize the baby in always. So we were asking the team to add in an extra task or an extra part of that golden hour. So we did think that that might be a challenge, but we do other admission swabs at the same time. So it all just became part of the swabs that the baby needed to have on admission anyway, training was ongoing. We started before the study began. By doing training for the senior team and then cascaded that down to more junior members so that we always knew that there was somebody senior on duty that will be able to run the test and gradually towards the end of the study, most people could do that. And that’s been the case as we’ve implemented it into our normal clinical practice since October of last year. And I think because the impact is so huge and we actually identified a baby within the first week of testing that was positive for the genetic change, I think that had a huge impact on the clinical workforce and it really drove home how important this was to become part yeah, really cool. So, yeah, quickly it quickly just became part of what we normally do. The other challenge, I guess, for us was we take all. The babies sometimes they don’t always just come straight from delivery suite. We transfer babies in that are sick and need specialist services. We just had to make sure that even if those babies had already received antibiotics, it became part of what we did for every single admission and we now test every single admission. Yeah, I think it’s quickly become embedded in what we do. And training just continues for new staff coming along or those members of staff that haven’t performed the test for a little while and just wants a refresher. The test isn’t complicated and like Gino has said, has become more simplified as time has gone on. And in hindsight, it feels a little bit like a lateral flow test. It’s a buckle swab of the inside of the baby’s cheek and it’s very soft swab. It’s really easy to do. And then. And you process it in not a dissimilar way, like I say, to a lateral flow, and then pop it in the machine and just start it going. And then you can continue with a normal routine admission process while the machine is running its test. And then just pop back and pick the results up off the device after 26 minutes. And then at that point, that is when the decision is made as to which antibiotics we then prescribe. So if the baby doesn’t have the genetic variant, we’ll just continue with our current guidance antibiotic, which is gentamycin, which is an aminoglycoside. And if the baby does have the variant, then we can choose a safe alternative. Yeah. I mean, again, this is just so cool. The first thing that really comes to mind here is it sounds like you’ve had success, right? In the first week you’ve flagged a child. That was very much. A candidate for an alternative type of antibiotic. So that’s super validating. And I know kind of reading through the study, it sounds like you’ve perfected this to the point to where you’re able to administer and get the results within about 26 minutes. Is that correct? Yeah. I think when we were designing the study, the key thing for us was to try why to choose outcome measures that assess the real world implementation of the technology. So we were very conscious as we were writing the protocol, that we didn’t want to come along and say, look at our fancy test. Isn’t it great? You can detect babies with the gene change, and it performs like this or like this. But then actually, if you could do all that but it was disrupting normal kind practice, and it was taking twice as long to receive antibiotics, or it wasn’t being used in the intended way, that actually that wasn’t a good intervention. And so our main outcome measure. Was, was the time to antibiotic therapy similar to previous practice, or were we extending time to antibiotic therapy? I think what we were able to demonstrate was that use of this new novel technology, nothing like this has ever been implemented before. It didn’t seem to disrupt aspects of normal care, which was what we were really pleased about. So obviously, identifying children with a variant and ensuring that they receive alternative antibiotics, that’s critical. But also, even for those babies who didn’t have a positive result, showing that it can be part of routine practice was really important for us. Yeah, I think that’s an excellent point. It’s a big difference between, theoretically, you can do all this, but actual in the real world, day to day of it, it sounds like Nikki and I had no idea that there was such broad swath of nurses that were being trained on this. I mean, it has to be something that can be integrated quite seamlessly into that process. Especially when you’re talking about. Delicate golden hour like that, which I have a follow up question here just kind of came to me. And this is a little loaded, but anyone can take this. What else is possible with this? And can you be testing for multiple genetic anomalies, if you will, at once? I mean, can we almost think of this as the ability to have a swab? And you test for not not necessarily just for things that would relate to hearing loss, but a full battery of tests? More or less. Are these Genedrive machines capable of sequencing for a variety of different things, or is it kind of a single application per test? Yeah, and I can take that it’s not necessarily sequencing, and it’s based on identification of this sequence, but it’s not sequencing per se, but technically, yeah, there’s no reason why you can’t look for multiple variants. And in fact, one of the follow on products that we’re working on again with Bill Newman and John, and the team is with a more complex test, that is for identification of non responders to a drug called clopidogrel in emergency care in stroke settings. But obviously that’s not the purpose of purpose today. But just to use an example, yes, it is possible. But as you go from the least complex to the most complex, I mean, remember, this is one single variant, and the challenges around implementation of that, getting it through adoption, getting it through UK approval, all relies on the simplicity of a clear actionable result. The more complex you become, that becomes much more of a challenge. And you take that to the extreme, like next generation sequencing, where you’re sequencing lots and lots of different things and the information overload just comes into play and it’s difficult to manage that. That information into clear actionable result. Great data, but difficult to work within time. Critical setting. So, technically, the answer is yes. We’re all very excited about this new emerging area of pharmacogenetic genetics, as John said, and there are many applications, but you also have to be very focused and make sure that you’re you’re measuring something that has a clear actionable result and there’s no ambiguity around it. For implementation and settings such as this, our team certainly see a world where these types of data so RnR 1, but other genes like Sip TC 19 and other pharmacogenes are available. When a page presents it’s embedded within records, or if it’s not embedded within records, you’re doing rapid tests to generate that information. But that information as utility. Across healthcare in different healthcare settings. So being able to have that information in an interpretable format and a clinically relevant time frame, which the Genedrive system can deliver, is critical. And we see it adding significant value and saving money for healthcare systems. Yeah, absolutely. It feels truly like the frontier of medicine. I’m so cool. So, on that note, I really appreciate you three coming on today to share about this study and how the implementation of it went and some of the different results. It sounds like there’s a lot more to come here on this. This is just getting started with what’s possible in this area. So thank you three for coming on and thanks for everybody who tuned in here to the end. We will chat with you next time. Cheers.
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About the Panel
Gino Miele, PhD, is the Director of Research and Development for Genedrive. In his role, he focuses on the development of in-vitro diagnostic assays and workflows that enable rapid sample-to-result nucleic acid-based point-of-care diagnostics and patient stratification. He primarily works on projects intended for resource-limited settings, such as HCV, TB, HIV, and HBV.
Nicola Booth, PhD, is the Research Nurse Manager at the Neonatal Unit at St. Mary’s Hospital in Manchester. With her expertise in neonatal care, she played a critical role in the development and implementation of Genedrive’s point-of-care genetic testing device for newborns at risk of hearing loss from aminoglycoside antibiotics.
John McDermott, PhD, is an NIHR Doctoral Research Fellow at the University of Manchester and a Clinical Genetics Speciality Registrar. He was appointed as the UK’s first Academic Clinical Fellow in Genomic Medicine in 2016. Working at the Manchester Centre for Genomic Medicine (MCGM) his research focuses on the application genetic and genomic technologies in the acute and everyday healthcare settings. As part of the Newman Laboratory he was awarded funding from the National Institute for Health Research (NIHR) to undertake the world’s first trial of a genetic test in the acute setting to avoid hearing loss in neonates.
Dave Kemp is the Director of Business Development & Marketing at Oaktree Products and the Founder & Editor of Future Ear. In 2017, Dave launched his blog, FutureEar.co, where he writes about what’s happening at the intersection of voice technology, wearables and hearing healthcare. In 2019, Dave started the Future Ear Radio podcast, where he and his guests discuss emerging technology pertaining to hearing aids and consumer hearables. He has been published in the Harvard Business Review, co-authored the book, “Voice Technology in Healthcare,” writes frequently for the prominent voice technology website, Voicebot.ai, and has been featured on NPR’s Marketplace.
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