00:00 – Prof Jenny Rohn: It’s been decades that we’ve had papers highlighting the inadequacies of some of these tests.
00:06 – If it doesn’t work, it doesn’t matter how cheap or convenient it is.
00:22 – Melissa: Professor Jenny Rohn is head of the Center for Urological Biology in the Department of Renal Medicine in the Division of Medicine at University College London. Her lab focuses mainly
00:31 – on understanding the science behind urinary tract infection, examining bacterial behavior and treatment failure using advanced human tissue models. She also collaborates with engineering,
00:40 – clinical and industrial colleagues to develop novel therapeutics. Thanks so much for joining me today to answer the questions submitted by our community.
00:47 – Prof Jenny Rohn: Thanks for having me on. Melissa: I’m excited to have you on because your name comes up a lot in our emails and in our socials.
00:54 – And so it’d be great to hear more about your research, but first can you share more about your background and how you became interested in UTIs?
01:00 – Prof Jenny Rohn: Sure. Well, I was, as you can probably tell from my accent, I was born in America. I was trained there. I got my PhD there.
01:08 – And I came over to the UK really interested in how our human cells react to various stresses
01:14 – and strains. And I spent quite a bit of time studying cancer, but I became a little bit disillusioned because there were about 10 gazillion people studying cancer around the world.
01:23 – And there were, I noticed that there were other diseases that hardly got a look in. And when I found out about urinary tract infection, I was really interested in
01:31 – the biology of it. Because as we may discuss later, it’s quite, it’s quite complicated how the bugs
01:37 – attack the bladder. And when I started looking into it, I thought, well, great, who’s studying this? And I did a Google search, as you do. And I discovered at the time, this is about 2010,
01:46 – I can only find about 12 labs in the entire world working on UTI, sort of at the molecular level.
01:53 – And I thought, this is ridiculous. And I thought I saw my calling. I thought this is a really great opportunity for me to apply my interest in cells, human cells, with something more worthwhile,
02:04 – and something that wasn’t being done a million times by lots of other people. So that’s how I got interested. And also as a woman, I’m really passionate about
02:11 – female health and particularly the way it seems to have been marginalized in research and also in
02:17 – clinical trials. So it’s sort of vibed with my feminist sort of outlook as well.
02:22 – Melissa: Well, that’s what we like to hear. And it has become such a big problem that we really do need more research in this space. And it’s always great to meet researchers who are focused on this.
02:31 – Today, we want to talk a lot about testing. So we’ve got many questions about that. So let’s just jump straight into it. What are the main reasons that urine dipsticks and standard urine
02:42 – cultures miss so many infections? Prof Jenny Rohn: Gosh, that’s a sort of a very complicated question. There are a
02:50 – lot of factors. Let’s just go through them. So first of all, when you get a urine dipstick or urine culture, you’re looking at urine. And if you think about your typical person who’s
03:01 – drinking lots of water, perhaps especially if you have UTI symptoms, the first thing that
03:07 – they tell you if you call 111 is drink a lot of water. So by the time you get to the doctor and
03:12 – you produce your urine specimen, it tends to be highly dilute. And both of the tests that you
03:18 – mentioned, the midstream urine culture and the dipstick are based on concentrations of stuff in
03:24 – the urine. So if you’ve just drunk three liters of water, you’re not going to test very strongly on
03:30 – either of these tests. And the dipstick has particular problems. I think it measures three
03:35 – things that could be relevant for UTI. It measures whether you’ve got the presence of
03:41 – white blood cells in your urine, whether you have the signature of particular bacteria like E. coli
03:50 – or klebsiella, these are particular kinds of bacteria. It doesn’t look at all bacteria, only a particular
03:55 – kind. And then also whether you might have trace elements of blood in your urine. So those are the three main things you would look at in a dipstick. All of these are quite insensitive anyway.
04:04 – Then you’ve got your highly dilute sample. And you’d be lucky if you would twig on any of those
04:11 – three parameters. And then if you don’t have the right kind of bug, for example, if you’ve got an
04:17 – enterococcus or staphylococcus or something like that, that’s not going to even be picked up by that bacteria pad. So already you’re looking at a situation where the deck is stacked against you.
04:28 – If you’re lucky enough to get a positive dipstick and your doctor believes that you need to have
04:34 – a urine culture, you’ve got the same problem. Highly dilute urine will have fewer bugs
04:39 – than concentrated urine. And also the samples that go off to the lab, they might sit there for a while.
04:46 – They get sort of cultured under conditions that are very, very good for particular bugs, again, like our friend E. coli, maybe not so great for other kinds of bugs.
04:56 – So you may not reach that magic threshold, whatever that might be. Usually it’s 100,000 bacteria per
05:02 – mil. Some labs do less. But there’s always a threshold cutoff. And if you haven’t achieved
05:09 – that for whatever reason, in some cases, because you’ve drunk too much water, then you’re going to
05:15 – get a negative test. Your test might also get thrown out if you’ve got a mixed growth. So that’s
05:21 – when you test for more than one bug. Historically, this has been seen as, oh, there’s something wrong
05:26 – with the sample. Let’s just chuck it in the bin. Whereas we now know that it’s highly biologically
05:33 – possible that you can have more than one bug causing an infection or more than one bug can be hanging out in your bladder and it doesn’t invalidate the test. So these are some of the
05:42 – reasons why both of these tests aren’t very good. Melissa: Right. And there’s multiple problems. So it wouldn’t
05:47 – be enough just to lower that threshold to cater to the concentration issue when it’s not picking up
05:52 – some of the organisms. Prof Jenny Rohn: Yeah. The problem with that, of course, is that we now know that the healthy
05:58 – bladder contains a microbiome, not surprisingly as the urethra is open to the environment and these
06:05 – bacteria can, they go anywhere. Bacteria will go anywhere where they can get. And you start getting
06:10 – into the territory of low level friendly bacteria that are in there. So once you have a very low
06:17 – count, there is the danger that you might start picking up the normal microbiota. And in that
06:23 – case, then that also complicates things because you might have a mix, you’re more likely to have a mixed growth, which is going to be chucked out. Or you actually don’t know if it’s a pathogen or not.
06:33 – So I can see why you need a threshold, but it’s, yeah, it’s a really difficult problem.
06:40 – Melissa: Yeah, it’s something that a lot of people in our community have come up against, the negative test results despite their symptoms of UTI, even if they’re very familiar with what a UTI feels like.
06:48 – And so it’s constantly a source of frustration. But there haven’t been much published on these tests and how inaccurate they are.
06:56 – Prof Jenny Rohn: There have been papers. There’s been quite a few papers throughout the history of the science. And I have to say that I find sometimes the medical
07:07 – profession is a bit conservative with a small c. So it takes a lot of research until findings from
07:15 – science filter down into medical practice. And that’s probably a good thing because you don’t
07:20 – want to rush into practice things that don’t work, that aren’t cost effective, especially with the national health where money is a serious problem. So yes, I can understand why it takes a while for
07:32 – these things to trickle down. But it’s been decades that we’ve had papers highlighting the inadequacies of some of these tests. But since we’ve got nothing really better, I think it’s,
07:43 – and especially the dipstick, and the dipstick is compellingly lovely. Like it’s a little piece of paper as cheap as chips. It takes like 30 seconds. It gives you an answer yes or no. And I can see
07:56 – why that’s very compelling. But equally, if it doesn’t work, it doesn’t matter how cheap or convenient it is.
08:01 – Melissa: And it leaves patients in this situation of not being able to get treatment because there was nothing to base the treatment on, and then also not being able to get better testing in
08:09 – order to find out what is the problem, even if it isn’t an infection. Prof Jenny Rohn: I understand that the dipstick is often a gateway to getting a midstream urine culture.
08:17 – And I guess in that case, yeah, it could
08:24 – prevent you from getting another test, although that test isn’t that great either. But it’s probably a bit better than the dipstick for sure.
08:31 – Melissa: Yeah. And with regards to the quality of a sample, do you think a catheterized sample is actually better than a midstream urine? Or does that run the risk of then
08:39 – missing infections lower in the urinary tract? Prof Jenny Rohn: Well, we don’t know much about, you know, if you
08:47 – have a UTI, it’s really difficult to say where these bugs are. They could be in the bladder,
08:54 – they could be in the urethra. There haven’t been a lot of studies about sort of looking at the
08:59 – different niches of UTI. It’s always presumed that the bugs are in the bladder. But of course,
09:05 – they would maybe in the process of ascending, right, they have to come from somewhere, they’re coming from the gut ultimately. So they could be in there. If you have a catheter specimen,
09:12 – I mean, one of the problems is of course, catheters can introduce the risk of getting a UTI. So if
09:20 – you get a catheter, first of all, it’s incredibly uncomfortable. If you’ve ever had one, you’ll know it’s excruciating. I don’t like urinary catheters, but if you get one, so you could be damaging the
09:28 – tissue and promoting infection. You could be introducing new bugs by doing that. And also,
09:34 – I mean, we’ve, we and others have done studies showing that, you know, if you use a catheter, you can see bugs. So we know they are in the bladder. I don’t know if it’s any better. The whole,
09:45 – I mean, maybe it’s nice to have the whole niche there, including the urethra. Melissa: Most patients would prefer not to have a catheterized sample if think they can avoid it.
09:52 – Prof Jenny Rohn: Right. Melissa: Yeah. Prof Jenny Rohn: Yeah. Melissa: Well, I guess there’s a lot of problems with testing. And so sometimes patients
09:58 – just end up getting treatment based on no testing because it’s empirical. If the antibiotics do then
10:04 – work in that case, would you say that’s a good indication that an infection was present? Prof Jenny Rohn: I would have thought so. I mean, we can discuss the caveats here, which is of course,
10:14 – the placebo effect. So, you know, you’re getting a drug, you might feel a bit better because of that.
10:21 – Just what they call sort of regression to the mean, or that’s a fancy way of saying, well,
10:26 – maybe you were going to get better anyway. You’ve taken these pills and you’ve gotten better. It does improve you had an infection. But if you feel really a lot better quite quickly,
10:36 – it is a good indication that there probably was something there. But you never know. You never know. Melissa: That’s true. I think a lot of patients can probably tell. And that’s one of the things that
10:46 – we come up against that the patient reported symptom is not taken very seriously in research.
10:52 – And so I think that we really need to put more weight on that given the lack of accuracy in testing. Prof Jenny Rohn: I mean, we do see in a trial – clinical trials that I see,
11:02 – things are getting better. So there’s almost always a quality of life assessment. So before and after treatment, you’re asked to fill in a questionnaire about how you feel, what your symptoms
11:11 – are, what’s your day-to-day life like. And so patient quality of life is being taken increasingly
11:16 – seriously as an endpoint in clinical trials, which is great, right? Melissa: So important. Prof Jenny Rohn: Nobody ever used to care of it. But any self-respecting researcher is going to have that kind of
11:26 – patient-focused output. Maybe you’re testing whether the bugs have gone down or you’re testing
11:33 – whether the white blood cells have gone down. But if you don’t test if the person actually feels better, how good is that treatment? So yeah, I think things are moving in the right direction.
11:42 – I think quality of life assessments are taking more and more of a center stage with outputs, pre-trials.
11:48 – Melissa: Yes, it’s really good to see that change. When it comes to different technologies of testing, what are your thoughts on more advanced methods like next-generation sequencing? Do you think
11:57 – they can provide useful information? Prof Jenny Rohn: So the problem with next-generation sequencing is, first of all, it’s horrendously expensive. And at the moment, we don’t have one in every
12:06 – GP surgery. And it’s used in hospitals. But we get the same problem that we have with –
12:11 – when we were discussing the microbiota and the sensitivity. So if you do next-generation
12:18 – sequencing on anybody’s urine, you’re going to find bugs. There will be bugs in there. Even if you’re a man, there will be some bugs. So then you have this long list of bugs.
12:28 – And then you’re asking yourself, what’s the pathogen? Is it necessarily the one that’s got
12:34 – the most? Or maybe there’s one of those guys in the list is doing the job, but he’s just
12:41 – more effective at it. So he can cause more symptoms at a lower level. We don’t know enough about the
12:48 – normal signature of the microbiota, really, to be able to just look at these printouts and say,
12:54 – oh, yes, this is the signature of a perfectly healthy person. Oh, no, this is the signature of a chronically infected person. And that is the culprit. So until we do enough studies to understand
13:04 – like the vast variety of ecology that’s seen in different people’s waters, it’s going to be really
13:12 – hard to use that tool, I think. Melissa: Yeah, we get that question a lot about whether something on a test,
13:18 – how do you know that it’s actually causing the symptoms just because it’s there? And in that case, a lot of people get high lactobacillus on certain test results. And does that mean the
13:28 – lactobacillus could be causing a problem? Or do we just not really know what’s causing the problem?
13:33 – Like you said, from a long list. Prof Jenny Rohn: Well, if it’s lactobacillus, it’s probably friendly. So lactobacillus
13:40 – is the most common bacteria in the female uro-microbiota. So you would expect to see lots of
13:47 – lacto up there. And if I saw lacto in my bladder, I’d be thrilled because I would assume it’s probably doing something good or at least it’s neutral. Lacto plays an incredibly important role,
13:57 – it’s thought, in protecting especially women from UTI, usually in the vagina where it’s sort of the
14:05 – last outpost of resistance before you hit the urethra. But we don’t really know what they’re
14:11 – doing in the bladder. They may be passive passengers or they may be actually protecting the bladder
14:16 – from UTI. That’s one of the things that our lab is actually looking into now. Really interesting stuff. I don’t know the answer. But I think, yeah, but that your example is great. Like if you get
14:26 – massive amounts of lactobacillus, is that causing UTI? I kind of guess not. But again, who knows?
14:33 – Because bacteria never stops surprising me. You might think it’s a friendly bug, but maybe it’s
14:39 – gone rogue. Melissa: Yeah, for some people, it could be the problem. Prof Jenny Rohn: Exactly. So I don’t want to say, you know, never. But I wouldn’t be too worried about that. But then, yeah.
14:50 – Melissa: Hopefully for most people, that is the case, that it is protective. So we don’t need to worry about that. And there’s also a question
14:55 – often brought up about interstitial cystitis. And do you think that that might be – it might be the case that that is actually a missed infection given the problems with testing or a biofilm or
15:05 – embedded infection that’s just not being picked up?
15:10 – Prof Jenny Rohn: The definition of this disease is usually includes – excluding infection. So if you’ve got no measurable infection, the algorithm would tell you
15:20 – to go down another route, which could include IC. I don’t know much about IC, to be honest.
15:26 – It’s not my area of expertise. But of course, if you have symptoms and no measurable bacteria and
15:33 – the tests aren’t very good, these people might have a hidden infection, of course. But there are
15:39 – other options. They may have no infection. And it’s caused by something else that is very possible, because this is an inflammatory disorder. It causes – lots of things can cause inflammation.
15:48 – And then there’s also some evidence that if you have a UTI and then you completely clear the UTI,
15:55 – you could still have symptoms. There’s evidence from humans and there’s evidence from mice. So some of these people that aren’t responding to antibiotics, it’s possible a subset of them are
16:04 – just hit and run. Post-UTI, it’s kind of like the post-viral thing, like long COVID, you know,
16:11 – you can get infections and afterwards the infection can be long gone and you can still have symptoms.
16:17 – So that could be another thing. It’s like the body was reacting to the bacteria, reacting so strongly that even after the bacteria got cleared, it didn’t get the memo to stop reacting.
16:27 – And I think that could possibly explain some of the unfortunate people that don’t respond even to
16:32 – long-term antibiotics. But there’s so much we don’t know. And of course, mice are not people. You can do all sorts of clever things with mice. The good thing with mice, this is going to sound
16:42 – awful. Sorry, I don’t work with animals because I think it’s wrong. But if you have an infected mouse
16:48 – and you treat it with antibiotics, you can literally grind the whole mouse up and prove
16:54 – that the bacteria are gone. But if those mice still have symptoms, like you can poke them with a little stick and they twinge and they urinate more frequently after having a cleared UTI,
17:04 – it does make you wonder really. I mean, mice aren’t people. They’re very different in some ways, but there is some evidence that even a cleared infection can still leave you with lingering
17:14 – inflammatory symptoms, which is disturbing really. This is why we need to know more about it, because you might have two classes of people. You might have the bona fide, chronic UTI, recurrent
17:26 – UTI, it’s not going away, it’s embedded, it’s in a biofilm, you can’t detect it. They need to be treated somehow. And then you might – in an antimicrobial way. And then you might have another
17:35 – subset of patients who have a post-infection inflammatory response and maybe those people
17:40 – need something else like steroids or another way to sort of dampen the immune system. And it’s
17:46 – totally not antimicrobial. And we have no way because the tests are so bad. You can’t grind
17:52 – up a person and prove they’ve got no bacteria like you can with a mouse. Sorry to gross people out. I shouldn’t talk like that. Really, it’s how on earth can we tell the difference between these
18:01 – two types of people without more research into it. Melissa: Yeah, and I think that kind of highlights one of
18:07 – the problems that the same approach is used regardless of your experience. We don’t have good guidelines for how to treat these patients that have had the problem for such a long time, but maybe you could
18:16 – talk a little bit more about why antibiotic treatment does fail for so many people. Recurrence
18:21 – happens with these chronic infections where people have continuous symptoms. Prof Jenny Rohn: Yeah, so there’s obviously – there’s a sort of a
18:28 – continuum of recurrent or chronic UTI. You get people that get
18:33 – massive UTIs and then nothing. And they’re totally fine for a couple of months. And then you get people with constant low-grade symptoms. I think these are all in the same spectrum
18:43 – of bacteria that are not responding to antibiotics very well. And there’s so many reasons why I
18:48 – could just hit a few scientific reasons why. So you’ve mentioned a few already because I’m really pleased by how well educated the patient population is. You all know about embedded
18:58 – infection. So these bacteria are very good at diving into the bladder wall, taking up residence inside the bladder wall where they cannot be cleared by either antibiotics or the immune system.
19:07 – And actually, usually antibiotics work in conjunction with the immune system. You need kind of a healthy immune system and antibiotics to really clobber it. But if they are intracellular, as we
19:18 – call it, or inside the bladder wall, there’s nothing you can do until they eventually will turn
19:23 – over. The bladder is like a conveyor belt. So the cells at the bottom move up and eventually they get shed into the urine. Eventually, I suppose, if you treated somebody long enough, you might
19:32 – theoretically get rid of all those reservoirs. But most people only get three days of nitrofurantoin
19:39 – if they’re lucky. Melissa: Yeah, it’s not a lot. Prof Jenny Rohn: That’s not going to happen. And then you have the case where you mentioned the biofilms we can have, and we do see biofilms in human cell models. So we
19:50 – know that they’re there even without a catheter. We know that you can get biofilms in the bladder. And biofilms are notoriously resistant to antibiotics, not just because they have this slimy
19:58 – outer layer that prevents the drugs from getting in. But when you’re biofilm, you’re kind of asleep.
20:04 – You’re not dividing, you’re just hanging out, you’re dormant. And almost all antibiotics work by targeting some active process like cell division or metabolism. And if your bacteria is not
20:14 – metabolizing, even if the antibiotic gets to it, there’s nothing to act on. So biofilms are a
20:20 – particularly difficult nut to crack. So that could explain recurrent infections. Then you’ve got,
20:26 – of course, this whole range of really weird and wonderful things that bacteria can do in the presence of antibiotics. If they’re just floating there in the urine and they’re exposed to antibiotics,
20:35 – some of them can sort of get around the antibiotics for a while by switching their genes on and off.
20:42 – And then when they do that, they can sort of temporarily not get killed and live to fight
20:47 – another day. So the minute the antibiotics are gone, they’re back. They go back into their normal mode. This is called resilience. It’s really hard to study. And it does happen with lots of
20:57 – different bacteria. So we’re pretty sure it’s happening. But yeah. So those are three major
21:02 – reasons I think why people might respond. And of course, there’s a fourth one that people don’t often think about, which is your own genetics. As I mentioned, you need a healthy immune system as
21:11 – well as drugs to really work together to clear a really embedded infection. And some people may not
21:18 – have the best genetics for that. We know that UTIs can run in families from mother to daughter.
21:25 – It’s been shown that there’s some mutations in particular genes, especially genes that are sort of sentinels that look out for bacteria. Mutations in those genes can lead to a reduced immune system,
21:36 – which might give you problems. And of course, people who are immunosuppressed, like patients with renal transplants, for example, they get loads of UTIs. So that’s
21:45 – another reason. Maybe your immune system is just not up to scratch. And then again, this sort of
21:52 – goes back to your point that we need to know why the UTI is not being cleared to treat it properly.
21:58 – So if it’s an immune problem, then you might want to consider immunotherapies or something else
22:03 – that doesn’t actually unfortunately exist yet. But at least you could do research and try to find
22:09 – a therapy for that problem. Melissa: It would be good if there was more investigation into root cause for different patients, because we see so many different experiences in our community. And a lot of people
22:19 – ask whether it’s a re-infection. So are they having an infection constantly seeding from their gut? Or could it be something in their environment? Do you think there’s like a, how many people
22:27 – do you think will be in that boat versus those who might have the chronic infection that it’s just not being cleared properly?
22:33 – Prof Jenny Rohn: I think that all of those scenarios are completely possible. You could have people who have a reservoir in their gut and they keep getting reseeded,
22:43 – that’s re-infection. You could have people with a reservoir in the vagina, especially in postmen
22:48 – or palsy women who don’t have estrogen. You can get, you can get a nice sort of cozy place for them to hang out and regroup because being in the bladder is no picnic. You’re in this place and
22:58 – six times a day or 12 times a day if you have a UTI, you’re getting flushed out. So the vagina is a nice safe place where they could hang out. They could be hanging out in the
23:06 – bladder wall, another nice safe place. So but telling the difference between those, you could do
23:13 – tests on stool, on poo and sort of compare what’s in poo versus what’s in the bladder.
23:19 – People have done those studies and they have shown that people who get UTIs, it can be preceded by
23:25 – this massive bloom of bacteria in the gut. So yeah, that could be the case as well. And I don’t
23:32 – even want to suggest it’s down to bad hygiene. I mean, I think that particular accusation has been
23:39 – weaponized against women. Melissa: We need to put it behind us definitely. Prof Jenny Rohn: It’s really hard to control the movement of bacteria. In a tiny little space from anus to urethra where there is lots going on,
23:51 – you might be having sex, you might be wearing jeans, there’s sort of rubbing, you’re riding a bicycle, you’re just walking, you’re just existing. And of course, it’s not that you haven’t wiped from
24:03 – front to back and taken a shower. There’s been some really shocking things, levied at women and their hygiene regimen, which really makes me angry.
24:12 – Melissa: Yes. Prof Jenny Rohn: It’s really hard. Melissa: This deflects from the real problem, which is that we haven’t done enough research to know why this is an issue for so many
24:18 – people and how to fix it. Prof Jenny Rohn: If a man had a urethra that was one inch from their anus, they’d be
24:24 – getting lots of UTIs too. And maybe this wouldn’t even be a problem because there would have been a lot more research a long time ago.
24:29 – Melissa: They probably wouldn’t be blamed for it either. But speaking of treatments, what do you think the future of UTI treatment will look like?
24:38 – Prof Jenny Rohn: Well, there’s some exciting things on the horizon. I can touch on, I mean, your community is so well
24:45 – informed. I think the friendly bacteria angle is really strong. I am a firm believer that the
24:53 – microbiome may have the power to cure all ills, maybe not on its own, obviously not on its own,
24:58 – but if we could maybe engineer it to be a little bit stronger, we’re synergized with antibiotics.
25:05 – There are some antibiotics that don’t kill lactobacillus by nature. So lactobacillus is naturally
25:11 – resistant to, for example, trimethoprim. Not used so much anymore, trimethoprim, but it doesn’t kill lactobacillus. So you could imagine some sort of therapeutic scenario where you get a probiotic
25:21 – lactobacillus in conjunction with an antibiotic that doesn’t kill lacto, and maybe they can work together with your immune system to be more efficient at clearing bacteria. So that’s one possibility.
25:33 – Melissa: Patients would be quite interested in that approach too, because we do get a lot of questions about probiotics and how to rebuild the microbiome after antibiotic treatment.
25:41 – With all the side effects that come with that type of antibiotic treatment, there’s a lot of interest in other approaches.
25:48 – Prof Jenny Rohn: Yeah, I don’t know how much, there have been a few, there have been about, I don’t know, a dozen studies with lactobacillus in people,
25:54 – either through oral pills or through vaginal suppositories or pestories. And I think two –
26:05 – two out of the dozen showed some modest improvement. But none of these studies were very – they were
26:12 – small studies, and all the studies used a different bug or different protocols. It was really hard
26:17 – to compare between them. And we’re not sure whether the bugs are getting into the bladder.
26:22 – So it’s been shown interestingly, if you take a pill, a lacto pill, it ends up in the vagina,
26:28 – which is not surprising and good news. But does it get into the bladder from there? I would say
26:34 – maybe it would, because we wouldn’t have lots of lacto in our bladder as women if it wasn’t coming from somewhere.
26:39 – Melissa: It has to come from somewhere maybe. Prof Jenny Rohn: It’s a vaginal bacteria. So I think there’s a, there’s a, you know, but you need to know what strain do you use, do you use a cocktail of strains?
26:48 – You need evidence-based understanding of what is the best lactobacillus to put in there. There’s
26:54 – like hundreds of different species – strains out there. We don’t know the best one for this job.
27:01 – And then, you know, what’s the best way to deliver it? Is it really better to get a pessary in your vagina? Do you want to get a catheter and stick it straight in the bladder,
27:09 – where it’s most needed? Don’t know. We need lots of studies like these to work out the best, right?
27:16 – But I don’t think it’s beyond the realm of imagination to think that one day we can cure a
27:22 – lot of diseases, not just UTI, with bacteria that we’ve engineered to be a bit more effective.
27:29 – What a wonderful way, right? It’s like, sorry to interrupt, just because the chances of getting any side effects from this are very slim. And it’s like harnessing something natural just to
27:37 – make it a little bit better. Melissa: Yeah, I think patients will be interested in that type of approach, but it likely needs to be more personalized because every patient is coming from a different
27:46 – history of the different microbiome. So that could also be an issue with some of these smaller studies. They’re not stratifying patients into groups. They’re just looking at everyone
27:54 – as the same patient and applying the same method. But we hear a lot of anecdotal evidence in our
27:59 – community that people have found benefit from using certain types of probiotics. So I think it is worth that research being done.
28:06 – Prof Jenny Rohn: Yeah, absolutely. We just need more research. The bar is pretty low, actually. If you want to study a new medicine, a novel drug, the regulatory hurdles are really
28:16 – high. But to study probiotics, they’re kind of in a special category, and it’s easier to do trials with them, especially if they’re categorized as nutritional supplements. You don’t really need
28:26 – much to do those things. But of course, the nutritional supplements might not be the best combination.
28:31 – Melissa: Right. Prof Jenny Rohn: I don’t know. Melissa: Hopefully, we’ll see more in that space then. Prof Jenny Rohn: Yeah. I mean, other things to think about, I think the Uromune vaccine looks quite promising.
28:40 – There’s been some really promising clinical data. It doesn’t seem to be available on the NHS yet in this country.
28:48 – Melissa: Not yet. Prof Jenny Rohn: But in other countries, it’s being used widely. It’s being used in trials here in the UK, including in my department. So I think it might be rolled out at some point.
28:59 – Melissa: That would be great. Prof Jenny Rohn: There was some really amazing – so this is not peer review, but it was reported
29:05 – at a conference a few years back, a nine-year follow-up study of patients on Uromune.
29:11 – It was really interesting. Half of the patients responded amazingly well. And the other half, nothing.
29:19 – This goes back to your point, actually, Melissa, that different patients might need
29:24 – different things. But how exciting that half of the patients. Melissa: Amazing results for them. Prof Jenny Rohn: After nine years. Yeah. So, yeah.
29:31 – Melissa: It’s worth trying, but it would be good if we could identify what types of patients it would likely help, because at the moment, it is hard to access and it’s expensive. So we hear a lot of mixed feedback
29:41 – from our community, but a lot of people who found it quite beneficial. Prof Jenny Rohn: Oh, really? That’s good to hear, because I’ve not really heard. I’ve heard rumors that it didn’t work for real for people
29:49 – who are really bad, embedded infections, it didn’t do much for me. I heard one or two people say that,
29:54 – but I’ve never heard anyone saying, actually, it’s all right. So you have heard positive reports. Melissa: We’ve definitely heard both sides.
30:00 – Prof Jenny Rohn: That’s great. Melissa: And we have heard many positive reports. So even people who say it reduced the frequency of the UTI, which is a big deal for quality of life.
30:07 – Prof Jenny Rohn: Yeah. So that’s amazing. I’m glad to hear that. It’s a shame that they had to pay so much, and
30:13 – not everybody can afford that. But I suppose the NHS really needs to – they have to evidence base their
30:21 – choices. But I think there’s a lot of evidence now. So I’m not sure what’s the holdup, but I’m not an expert in.
30:27 – Melissa: We’ll keep an eye on it, because they use one of the – Prof Jenny Rohn: Nice and how they approve things. Melissa: Most frequent questions we get is, can I access Uromune in my country,
30:34 – and how? And in most countries, we just don’t have the information yet.
30:39 – Prof Jenny Rohn: I think I googled it once. In the UK, you can get a private appointment. I don’t know how much it costs.
30:46 – Melissa: Quite a lot. It’s quite a lot still. So it would be great if the NHS can take it on board at some point.
30:52 – Prof Jenny Rohn: If you just look at, make the economic case, the sheer number of antibiotics that are
30:57 – used, all the sort of clinic visits and tests that are done that are useless.
31:03 – Melissa: Exactly. Prof Jenny Rohn: If you could prevent even a fraction of those, I would imagine there’s a good business case.
31:09 – Melissa: I think there is. Prof Jenny Rohn: I don’t know. You’d have to crunch the numbers. But to me, it seems like a no-brainer. I guess maybe the definitive phase three trial hasn’t been published. I don’t know.
31:18 – I don’t know what the holdup is. It’s not holding up Europe. They’re just all using it now.
31:25 – Melissa: Yeah, it’s much more accessible in Europe. But speaking of novel therapeutics, what are you working on in that space?
31:31 – Prof Jenny Rohn: Oh, that’s exciting question. So we decided to target the intracellular
31:38 – bacteria in the biofilms. Because we think that maybe not for every patient, but for quite a few patients, that’s probably one of the issues. Antibiotics don’t penetrate the bladder wall.
31:49 – Some do. There’s a few classes of antibiotics that can, but they’re not the ones that are normally indicated for UTI. So we thought, wouldn’t it be great if you could take a bog standard, really
31:59 – decent antibiotic like nitrofurantoin, which has an excellent safety profile and has been used for
32:04 – almost 60 years and the resistance is really low because it has multiple modes of action. Whenever a drug has more than one way to do something, the bacteria struggle to resist it. So nitrofurantoin
32:14 – has an excellent profile. The only safety issues it has has to do with issues with the lungs.
32:21 – So that’s because you’re taking it as a pill and your entire body is being dosed. And of course, your entire microbiome is being dosed by nitrofurantoin. So you might get stomach issues,
32:32 – you might get lung issues that are quite serious actually. But what if you could put the nitrofurantoin directly into the bladder and make it penetrative enough so it could go into the bladder
32:41 – wall and kill those bacteria and bust up the biofilms while they’re at it. That’s what we thought. We thought that’d be a great idea. UCL was working together with Oxford on this and we
32:50 – quite some time ago, as you probably know, we came up with this solution called CapFuran,
32:56 – which are micro-encapsulated nitrofurantoin. Little spheres, they’re about five microns.
33:02 – For reference, a bacteria is about two microns. So if you were a bacteria, CapFuran would be the size of a car. So it’s a massive thing. So these are not intended to go
33:12 – into bacteria. They’re intended to go into cells. And the cells then, so they’re like a balloon
33:19 – full of antibiotics and they float down, dock onto the bladder wall, and then they push the drug into your cells and through the bladder urothelium without the capsule going in,
33:30 – which is great because the capsule’s made up of, although it’s a biodegradable, non-toxic polymer, you really don’t want that stuff coming up your cells. So it’s great that
33:39 – they just, and if you watch a video of this, it’s really cool. These capsules come in and they just,
33:44 – if you put some green dye in there to follow what’s happening, they go and they squirt it in, this is the cells all turn green, the capsules turn clear because they’ve emptied. And then,
33:52 – of course, they will be urinated out in your next wee or will biodegrade. And the nice thing about
33:59 – this, I have to say, I should say, and I should have said at the beginning, I have stock options in the spin-out company at UCL. So I take what I say with a grain of salt because I have a conflict
34:08 – of interest. But personally, having said that, I think it’s a really nice idea. I have really
34:13 – promising preclinical studies. And yeah, the idea is that the bacteria cannot escape from the drug
34:19 – if it’s being delivered in this way. Melissa: Is that something you would take orally or via a catheter? Prof Jenny Rohn: Unfortunately, it’s an what we call an intravesical treatment. It’s a catheter,
34:28 – which is right, not great. But on the other hand, you will not be dosing your lungs or your
34:36 – gut microbiome with this nasty antibiotic. So there’s a trade-off there. Yes, it’s a little
34:43 – bit uncomfortable. But we hope that you don’t need more than a couple of squirts of this.
34:48 – We don’t know the regimen yet. Melissa: I think a lot of people are okay with that kind of treatment. We get many questions about intravesical treatment options, and they just aren’t a lot for this
34:58 – patient population. And they would be interested if it was successful. Prof Jenny Rohn: They already get GAG, you know, hyaluron and other GAG instillations, and some of them get intravesical, gentamicin
34:09 – treatment. So we actually did some market research because we were curious. We got a grant and did
34:16 – a big survey in the US and the UK, just simply asking people, if you had a treatment that
34:22 – worked, would you mind having a catheter? And most people are like, bring it on. It actually works.
34:27 – Yeah, the acceptability seemed to be quite high. So yeah, that is the trend. We are doing really
34:33 – well. But the problem, of course, is funding. It’s very hard to convince investors that this
34:38 – women’s disease that’s not breast cancer, it’s not killing lots of people, it’s hard to convince
34:45 – people that they will make a return on their investment. So sometimes I go to these investor meetings and it’s a whole sea of Hugo Boss suits, and there’s me up there trying to convince them
34:55 – that this is important. I usually manage it because I say, think of your girlfriend, think of your
36:01 – wife, think of your grandmother. There’s a lot of people suffering from this. And I think,
36:08 – yeah, we have some really wonderful benefactors. We just haven’t cracked that last funding round
36:16 – that we need to do the clinical trial. Also, we are manufacturing this product in a factory,
36:22 – which has proved to be difficult initially to scale up this to. We were doing it in a lab on
36:28 – a bench top, and now we have to make a huge – Melissa: Yeah, it’s a big change. Prof Jenny Rohn: Yeah, it’s taking a while, but I think
36:34 – we’ve cracked it now. So we’re just now putting together, hopefully, a nice package where we can raise some funds.
36:42 – Melissa: Have you tested this in humans already? Or is that what your next step will be? Prof Jenny Rohn: No, but the good thing about this from a regulatory point of view is it’s only two ingredients,
36:52 – nitrofurantoin, which of course is a generic, and the polymer, which is already in use in people
36:59 – as a contrast agent. So if you ever had an MRI scan, you may already have had this polymer. So it’s
37:06 – already approved for – FDA approved, MHRI approved. So the two ingredients separately are approved.
37:12 – And then if you think about anything that goes into a bladder, compared with putting it in your bloodstream or your gastrointestinal tract, it’s a privileged environment. What happens in the
37:22 – bladder stays in the bladder. Things don’t get out of there. So even if they were mildly toxic,
37:27 – which they aren’t, they’re never going to get out of the bladder space and into the bloodstream.
37:33 – So I think it’s got a really good chance of getting a swift, if it works, getting a sort of a swift regulatory approval. We were really hoping.
37:41 – Melissa: Yeah, and I think the patient’s, the patient reception for this type of therapeutic will be good as well. So if there’s any investors watching this video,
37:48 – maybe they can reach out to you. What is the best way for someone to get in touch with you? Prof Jenny Rohn: Just email me. Just Google me. I’m all over emails. Look at UCL’s website. You can get me on
37:56 – LinkedIn. You can get me on socials. Yeah, that’d be great. Melissa: Have you published any papers on this capsule?
38:03 – Prof Jenny Rohn: Yeah, it’s been published a few years back. You can read about it.
38:09 – Melissa: So if you can share the link with me, I’ll put them in the video description so people can find them easily.
38:15 – Prof Jenny Rohn: Yeah. So we tested this on our human bladder mini blot or sort of our mini bladder model,
38:20 – which is quite exciting. And we didn’t need to use any animals to test this because
38:26 – the two ingredients are so well known. Unfortunately, there does need to be a toxicity study in rats. It’s mandatory. We can’t get around it, which makes me sad because I don’t
38:38 – tend to work in animals. But yeah, just to prove that obviously you don’t want to put something in a person that hasn’t at least touched a few rats, I guess.
38:47 – Melissa: Yes. So we hear that about most things going to trial first. So this is unavoidable.
38:52 – Prof Jenny Rohn: But it’s actually good that we don’t have to test the efficacy in an animal model because I have to say the animal models for UTI are terrible.
38:58 – I probably have some mouse people listening maybe, not terrible, but there’s a lot of
39:03 – difference between humans and mice in the bladder. And imagine you had a brilliant new drug and you
39:09 – were forced to test it on animals to prove it worked and it didn’t work. But actually, it would have worked in people. This has happened quite a few times apparently. And vice versa,
39:18 – you’ve had something that was really highly toxic in mice and never went any further. But in a human, it wouldn’t have been. So the mouse as a gatekeeper has problems. So I was very pleased that we were
39:29 – given basically, it seems that we’ll be able to just circumvent that kind of test and just use our
39:35 – human mini bladder as the ultimate arbiter of whether it’s safe and effective. And then the
39:40 – inevitable road in trial just for the toxicity, which we can’t get out of.
39:46 – Melissa: If you can get the funding in place, what’s the timeline do you think until clinical trial?
39:52 – Prof Jenny Rohn: Yeah, so not too bad. I think we could even be looking at next year if everything lines up.
39:58 – Melissa: Okay, that’s very soon. Prof Jenny Rohn: Of course, you need to get approval and the funding and the approval and 2026, maybe 2027, I hope.
40:09 – Melissa: Okay. That’s exciting. Prof Jenny Rohn: We have thought that before and things – COVID really set us back.
40:17 – There are very few, interestingly, very few manufacturers of nitrofurantoin.
40:22 – Most of them are in India. The supply chain was, especially during COVID, was just a nightmare. And yeah, it’s interesting how interdependent all the countries
40:33 – are when it comes to drugs because people don’t really think about it. But a lot, many of the things that we take from our GP are produced in other countries and supply chains make a big
40:44 – difference. So for example, a few years ago, we were having massive problems getting HRT. I think it was estrogen. It was this massive shortage. Women were meeting in petrol stations to exchange
40:55 – spare pills. It was awful. That would never happen with Viagra, I have to say. But yeah, you can have supply chain issues and the pandemic was really terrible for our trajectory. It set
41:05 – us back a few years. But I think we’re back now. And hopefully – Melissa: That’s great to hear. Prof Jenny Rohn: If we can get the funding, hopefully it will fly.
41:13 – And of course, it may not work, right? Things may not work as you intended.
41:19 – Melissa: Hopefully that’s not the case. Prof Jenny Rohn: I have a good feeling, but I can’t say for sure. Melissa: Yeah, well, it’s great to hear the updates on that because we often get questions about what
41:27 – you’re working on. The patient community is quite aware of what you’re working on and very enthusiastic about joining a clinical trial once you get there. So I hope that you can get the
41:36 – funding in place and maybe this video can help. And we’re also happy to share any papers that you
41:42 – publish or anything else that might help to raise awareness about what you’re working on. Prof Jenny Rohn: That’s really kind.
41:47 – Melissa: Really wanted to thank you again for chatting to me today and answering all the questions that we received. Prof Jenny Rohn: You’re very welcome.
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