New Hope for Patients with Black Bone Disease - Nick Sireau, CEO and Chair of Trustees at the AKU Society


Just a few weeks ago we shared the story of John Crowley’s family and their battle with Pompe disease on Raise the Line, and in this episode, we’re honored to share another remarkable story of a rare disease parent and the contributions they've made beyond their efforts to help their own loved ones. Nick Sireau is the CEO and Chair of Trustees of the AKU Society, an award-winning patient group that helps people with Alkaptonuria (AKU), sometimes referred to as black bone disease, a rare disorder affecting both of his children. In AKU patients, a build-up of acid in the body leads to a painful breakdown of bones and joints, and serious heart complications. Nick’s tireless efforts have led to some extraordinary results, including making the very first treatment for AKU available. Nick is also Founder and Chair of Orchard, a medical charity that works to develop new and better treatments for obsessive-compulsive disorder (OCD), a misunderstood mental illness that Nick has battled for many years. Join host Shiv Gaglani for a fascinating look at the impact one parent has had on the welfare of so many, and for advice for those weighing career options in the healthcare field. “There are hundreds, if not thousands of these ultra-rare diseases that just nobody is touching.” Mentioned in this episode: https://akusociety.org/ https://www.orchardocd.org/




Shiv Gaglani: Hi, I'm Shiv Gaglani. Today we are happy to share another remarkable story of a rare disease parent and the contributions they've made beyond their efforts to help their own loved ones. Our guest is Nick Sireau, who's the CEO and Chair of Trustees at the AKU Society, an award-winning patient group that helps people with alkaptonuria or AKU, which is a rare genetic disease affecting both of his children. Nick is also the co-founder and chair of Beacon, an organization that helps all rare disease patient groups, and plays the same role at Orchard OCD, a medical charity that funds research into obsessive-compulsive disorder. Perhaps most impressive of all, he's involved in making the very first treatment of AKU available. 


Before we get started, I'd like to thank Philippe Pakter, who was a podcast guest, for highly recommending and connecting me to Nick, as well as a friend and former Elsevier colleague, Tim Hoctor. I learned over several conversations that Tim heard Nick speak at a conference and that was why Elsevier, in large part, got involved in the rare disease space in the first place. So, Nick, it's an honor to have you with us today.


Nick Sireau: Thank you very much. Good to speak to you.


Shiv Gaglani: So, in your own words, we'd love our audience to learn about your background, and what got you interested in the world of rare diseases? Was this something interesting before your children or after your children?


Nick Sireau: Yeah, absolutely. So, I really started developing an interest in rare diseases after the birth of my first son, Julian, in the late 2000s. When we brought him back from the maternity clinic on a Sunday, we noticed that his nappies were going red-black. So, we called an emergency doctor who tested for blood and didn't find any, and who asked what we'd eaten. We'd had some red cabbage that day, so he said it was the dye from the red cabbage entering the breast milk and then the baby and going into the urine. We were not very impressed by this answer, to be perfectly honest. 


The next day, we went to see our GP, who did a whole bunch of tests. He sent off for some tests at Great Ormond Street Hospital in London, and it came back with this diagnosis of this ultra-rare disease called alkaptonuria, AKU, which we now call black bone disease. Up until then, I wasn't aware of rare diseases at all. I had no idea that there were thousands of these rare diseases, and no idea that these diseases affect millions of people, and really no idea about alkaptonuria, which affects one person in roughly half a million. 


Our GP said, "Whatever you do, don't go on the internet." And obviously, that's exactly what we did. This was in late 2000. We came across loads of really pretty horrible stories of people suffering from AKU, this black bone disease, becoming severely disabled as life progresses. We were very alarmed and I got in touch with a patient in Liverpool called Robert Gregory, who had just made contact with a doctor called Dr. Ranganath at the Royal Liverpool University Hospital. Robert had convinced Ranga, as we call him, to set up a patient group with him and so he invited me to join and that's really when things started. 


So by then, my second son had been born. He was also diagnosed with alkaptonuria, and in 2003, we set up the AKU society which was the world's first patient group helping patients with this disease.


Shiv Gaglani: That's incredible. You obviously took fast action, and luckily, he got that diagnosis pretty quickly and didn't listen to that first GP about avoiding red cabbage.  One thing we've learned about the rare disease space is it takes an average rare disease patient four to nine years to get a diagnosis. That’s valuable time where they could be getting some therapy or a parent like you could jump into action and help develop a treatment. So, give us a bit more of a sense of AKU and how it affects patients. You already mentioned how rare it is. What are the palliative as well as the treatments that you're working on?


Nick Sireau: The first symptom is the urine going red-black. That is due to a certain acid called homogentisic acid, HGA, which accumulates in the body at two thousand times the normal rate. It's a single gene defect, so it's a monogenic disease. Basically, because of that mutation they have a certain enzyme called homogentisate oxidase enzyme, HGD, which malfunctions or doesn't properly form and because of that, they can't break down this homogentisic acid. Those who don't have AKU can break down HGA. Those with AKU, can't break it down. That acid accumulates and it binds to cartilage and bone over time and it goes black in a process called ochronosis and that's why it's called black bone disease.  


This takes time. It takes years, sometimes decades. Generally, in childhood, all you see is the urine, the sweat tends to go black, the earwax, and all that. But the real clinical symptoms, the painful symptoms, will tend to start in early adulthood and that will be problems of the spine and then the weight-bearing joints. The spine starts to collapse and fuse. All the weight-bearing joints will start to fall apart because the cartilage and bone starts to fragment. Bob Gregor, who founded the AKU Society, said it felt like having barbed wire in his joints. Then also the heart valves will start to calcify and people have bones in their eyes in their ears and different parts of the body. It's a multisystemic disease, as are most rare genetic diseases. We have one patient, for instance, who has had 12 joint replacements. He's had every major joint in the body replaced. Each time you go for joint replacement, it's a pretty significant operation. It does also affect lifespan. We see people dying earlier because of problems with the heart and all that. So, it's a pretty nasty disease, particularly painful, and of course there are all kinds of ramifications for mental health


Many of our patients suffer from depression or anxiety, or they will tend to lose their jobs because they can't work. Often their relationships will break down and all that. We had one patient who was sleeping on a park bench for ages until he got support from social services. So, it's a pretty nasty disease. Now, it's actually pretty well known amongst clinicians because it was the first disease to be shown to be inherited. There was a professor in London in 1901 called Sir Archibald Garrett who managed to show that AKU was inherited and that was the first time anybody had shown that a disease could be inherited. Until then, people knew diseases can be contagious, but no one knew they could be inherited and so he called it an “inborn error of metabolism” and there are now hundreds, if not thousands, of these inborn errors of metabolism. So, doctors will often remember that very vaguely from just reading about it in their kind of clinical history books and stuff, but that doesn't necessarily make diagnosis any easier. 


So you're absolutely right. Sometimes doctors will come with all kinds of reasons like red cabbage or whatever. If our patients are not diagnosed at birth, they will go on for years before the pain actually gets them back to see a doctor. Sometimes it can take ten, twenty, or thirty years. We had one patient where it took forty years before he had a diagnosis. They are sent from misdiagnosis to misdiagnosis, sent to psychiatric treatment because doctors don't believe them. It's pretty nasty, the whole diagnostic odyssey. 


So, what we've done when we set up the AKU society, is we did a lot of basic research into AKU. Even though people knew about it for more than a hundred years, our unscientific understanding was pretty rudimentary. As a patient group, I did lots of fundraising. We paid for a mouse model of the disease to be developed, which was very successful. A natural history study, a cell model, a post-mortem of a patient, and then there was a trial of a particular drug called nitisinone in the United States at the NIH. It unfortunately failed, in 2009, even though it was reducing the acid by 95% and patients on the trial were raving about it. But it failed, basically, because of a problem with the trial design. You know, it didn't last long enough, wasn't enough patients, the endpoints weren't really sophisticated enough. 


So, with the Liverpool group that we have put together with Professor Ranganath…well Ranga basically developed a whole kind of clinical development program, for nitisinone. And what we did then ten years ago, we applied for funding to the European Commission. We got six million euros in funding. We put together a European consortium, we managed to convince the company that owned the drug, Swedish Orphan Biovitrum, to join us, and then we did a phase two clinical trial and a phase three clinical trial, both of which were successful. They showed not only a reduction of 99.8% in the acid, but they also showed us statistical benefits in clinical symptoms and so Swedish Orphan Biovitrum applied to the European Medicines Agency two years ago, and they gave a positive opinion.  Then the European Commission gave them marketing authorization. So now all AKU patients in Europe and the UK can have access to this drug nitisinone. It's an absolute lifesaver, and both my boys are on the drug. I'm just back from Liverpool today with my son, Daniel, where he went for his week-long annual checkup for his AKU -- MRIs, X-rays, everything you can imagine -- and also, to renew his prescription for nitisinone. So, overall, it's gone really well. We're really happy.


Shiv Gaglani: That's incredible. What a great story and before we go deeper into that, and the pharma industry and thoughts on creating more rare disease drugs, how are your kids now? How are they doing? Can you give us any more background on them at this point?


Nick Sireau: Sure. They are aged twenty-one and nineteen. Our eldest has now been on nitisinone for four years. His dosage has just been increased, actually, and that's going really well. And Daniel, who's nineteen, has been on the drug now for two years. They don't have any of the clinical symptoms because, hopefully, the drug will have been started in time. The benefits of going to this national center that was set up ten years ago by Professor Ranganath in Liverpool is that it's a one-stop shop. What you need, particularly for ultra-rare diseases, is a real center of excellence in each country where you have a multidisciplinary team, you have clinicians, and rheumatologists and metabolic consultants, and orthopedic surgeons and everything who really understand the disease. Because until you have that, patients are sent from pillar to post. They go and see one doctor in one hospital, another doctor in another. There's no coordination. The doctors might have just seen one patient before in their whole career. It's just all over the place and that's why this National Center was set up ten years ago. So when the patients go there -- when my boys go there -- they have access to world-leading experts in AKU, which means that there's a better understanding of the disease, there's better monitoring, they can detect early signs of possible problems and all that and also, they can then prescribe the drug. So yeah…so far, things are going really well.


Shiv Gaglani: That's awesome, and these centers for excellence, Philippe mentioned as well. His daughter, Lysiane -- who was born in a normal French maternity ward -- did not get the best care immediately for Pierre Robin sequence. Ideally, they would have gone to the center in Germany. We have to make cross-border care -- which is a topic, I know he's been working very hard on -- more accessible. 


So, we're coming up on the fortieth anniversary in the U.S. of the Orphan Drug Act, which obviously, has really helped incentivize pharma companies to spend time developing treatments for rare disorders, like the one for AKU. I'm curious, what more can the pharma industry do to help for the other seven thousand zebras that exist?


Nick Sireau: I think there's a lot actually, and one of the problems is, there's pretty big market failure, I think, in rare diseases. I mean, obviously, pharma companies are profit-making businesses, but they will tend to avoid those diseases where they can't make a return on investment. They have investors who want to make their money back and all that kind of stuff. So, there are hundreds, if not thousands, of these ultra-rare diseases that just nobody is touching, because they're not managing to potentially get their investment back. 


I think there's a lot of things, actually, that pharma could do. I think they could look at alternative business models. For instance, the one that we developed was a public/private partnership. We got public funding from the European Commission, but the pharma company, Sobi, also put in some of their own money. They put in three million euros, compared to the EC six million, so it was a public/private partnership. They will make some money back from sales of the drug and all that. But now that the drug is off-patent and there are generics, it's obviously not going to be a blockbuster. 


One of the things I've been trying to tell pharma companies is that, yes, it's good for them to aim for their blockbuster drugs or their drugs that will generate significant revenue. But they should also maybe have one or two drugs in their portfolio where they're looking at maybe breaking even, or at some kind of low profits or whatever as a more kind of philanthropic approach. That'd be the first thing. 


I think the second thing is the pharma industry could look at what the legal industry does. All the big legal firms have pro bono departments which are funded by their profits and where they treat charities as full clients, but they don't charge them and I think the pharma industry could do that, too. There is one company in Cambridge -- in the UK, where I am -- called Costello Medical. They're an absolutely fantastic company. They do health economics and they have a pro bono department. They have done lots of work for us on AKU, for instance, on the AKU severity score index, which is one of the endpoints that we had for the trials. They've given us at least 80,000 or 100,000 pounds worth of pro bono support, and they treat us like real clients. I think if the pharma industry set up these pro bono departments, they could help rare disease patient groups by providing them pro bono support on clinical development plans, on all these kinds of things that we need help for. I think that's the second thing. 


The third thing I think should happen is I think that the pharma industry should be donating much more to patient groups. I mean, as patient groups, we're always struggling for funds. Most of our funds come from friends and family. We run marathons, half marathons, coffee mornings.  We get some support from trusts and foundations in the UK, from the Big Lottery Fund, some government funding from the NHS or from the European Commission. Very little comes from the pharma industry. The pharma industry gives very little money to patient groups for all kinds of reasons, which I don't really believe in, but we also have to jump through so many hoops. 


I'll give an example. We applied to a pharma company a number of years ago for like £10,000 to do a patient workshop. It took six months, loads of forms. In the end, we got £300. You know, it just was not worth the effort, and the administrative burden they put on patient groups is absolutely huge. So, what I believe they should do is they should put a small percentage of their profits into an independent foundation which would then provide support to patient groups and I think the best example for that is to see what the Chan Zuckerberg Initiative has done in the US. They were set up by the Facebook founder Mark Zuckerberg and his wife, Priscilla Chan. They put 99% of their shares into the Chan Zuckerberg Initiative and do all kinds of things, but one of the things they do is support rare diseases patient groups. Every couple of years, they do a call for proposals where they support twenty or thirty patient groups, and they give each patient group $600,000. Now with that money, you can recruit a couple of members of staff, you can do a scientific development plan, you can develop a registry, and you can start really interacting with the industry. That's what I believe pharma should be doing.


Shiv Gaglani That's really interesting. I like all those very actionable suggestions. We can't say all rare diseases are equal or all pharma companies are equal. There are certainly some pharma companies that are probably more ahead of the game than others in terms of thinking in this way.


Nick Sireau: That's absolutely right and the prime example is the company we worked with, Sobi, who I think were well ahead of the game, and I have nothing but praise for what they've done.


Shiv Gaglani: That's great. One point we'd like to make to our learners -- because many of them are current and future healthcare professionals – is why they should care about the zebras too, apart from clearly having stories like yours and John Crowley’s and David Fajgenbaum’s. We've had people like them on the podcast, too, where it's very motivating. You hear the passion, the voice. You get a lot of gratitude from these patients and patient groups if you dedicate your research career or provider career to these groups.  And the science underpinning why some of these disorders exist could elucidate applications well beyond that rare disease or that collection of rare diseases. 


The case we like to always share is actually the development of Castleman Disease drugs. David Fajgenbaum was telling me it led to a drug that has saved tens of thousands, or hundreds of thousands, of lives from COVID. Or, familial hypercholesterolemia led to the development of statins. I'm kind of maybe taking the wind out of the sails here, but I'm curious -- given all that you've done across many disease states, including AKU -- what can rare diseases teach us about common diseases and human biology?


Nick Sireau: Yeah, that's a key point and people have been saying that for hundreds of years. I mean, the founder of modern medicine, I think in the 16th century, said that understanding rare diseases helps us understand human biology. Sir Archibald Garrett, who discovered AKU as an inherited disease, said exactly the same and so did William Bateson, who was his contemporary, the father of modern genetics. So did Francis Collins the head of the NIH. So, people have known that for a while. 


A few things there are particular to AKU, and you gave some very good examples there. But AKU is an extreme form of osteoarthritis, and our studies in Liverpool of AKU have led to new discoveries in the molecular disease of osteoarthritis, which we published about a few years ago. So, it helps us understand the wider diseases and one of the reasons why I think is because rare diseases are often actually quite simple biologically, so they help us understand these biological mechanisms. 


But the second one -- which is really exciting -- we did a scientific workshop in Brussels in May and we had a scientific presentation from a group, Alvaro, from the Liverpool School of Tropical Medicine on this drug nitisinone, which we use for AKU. It was originally developed as a weed killer in the 80s and it works as a weed killer because it stops photosynthesis, and it works into the tyrosine metabolic pathway in plants. It was never commercialized as a weed killer because it was too potent. But an analog of nitisinone called mesotrione is one of the world's most successful weed killers, and you can buy it from any garden center. They then thought, well, if it works on a tyrosine pathway in plants, it should work on that pathway in humans. So they then developed it for a rare disease called tyrosinemia type 1 which kills children by age two, and is on the same pathway as AKU. That was in the early 90s. And then they thought, well, let's use it for AKU, okay, so it was repurposed for that. 


But more recently, in the past two or three years, this team at the Liverpool School of Tropical Medicine working with our Professor Ranganath is developing nitisinone as a way of controlling mosquitoes in developing countries because when mosquitoes take blood from someone who has taken nitisinone, the mosquitoes die. I don't understand the exact mechanism. They explained it to us and it's, I think, available online and there's an article on the Beacon website all about it. But it has something to do with the increase in tyrosine, which happens when you take nitisinone, kills the mosquito. What they are now trying to do is develop it as a medication that would be taken all across Sub Saharan Africa as a way of controlling the mosquito population. 


So, what you'd end up with is a drug -- originally developed as a weed killer, then developed for two rare diseases -- potentially now helping in the fight against malaria, dengue fever, and all those kinds of things. It's still a ways away but I think it's just incredible, actually, what can happen when you start studying rare genetic diseases. When we give the blood of AKU patients who've taken nitisinone to mosquitoes in the Liverpool School of Tropical Diseases, all the mosquitoes die, basically. First of all, they start to fly all over the place and they get paralyzed, and then they die. So, there really is something there that I think is worth exploring further.


Shiv Gaglani: That's amazing. I mentioned one of the guests that we had on the podcast is David Fajgenbaum who wrote the book Chasing My Cure. This week, he and I will both be attending the Clinton Global Initiative, for different rare disease-related reasons. He will be launching a drug repurposing initiative for that exact reason. Humans have discovered three thousand drugs, but we only have a very limited understanding of how many of them can be applied. So that's a wonderful example…of weed killer turned into something that's saving many people’s lives with AKU, and now potentially, in malaria treatment. 


Why you got involved with AKU is clear. How did the OCD connection come into play, and what are you doing with Orchard?


Nick Sireau: I have had obsessive-compulsive disorder, OCD, for just over thirty years, on and off. Sometimes really, really badly -- particularly six, seven years ago -- with an episode of incredibly severe depression which meant I had to leave my job and all kinds of problems. I don't know how much your listeners know about OCD. It's a very common disease. It affects about 2% to 3% of the population, maybe even more. In the UK, that's about a million to one and a half million. It is very trivialized by the media, by society, and even by the medical profession. The whole expression, "I'm a little bit OCD," really creates problems because the public perception of OCD is that it's just a quirk of personality. In reality, it's a devastating disorder. Fifty percent of patients have it very severely. One of my best friends took his own life two and a half years ago because his OCD got so out of hand. 


I run an OCD support group here in Cambridge. We have patients who haven't left their house for ten or fifteen years. One in ten patients with OCD will attempt suicide. Sixty percent are depressed. It's just awful. A lot of OCD is actually not the traditional types that people are aware of. So, people are aware of contamination OCD, they are aware of checking OCD, but there's a whole aspect of OCD -- which we call pure OCD -- which is really all in the mind where your obsessions and rituals are entirely in the mind and they tend to be linked to fears of doing harm, blasphemous thoughts, all kinds of things. 


I'll give an example. One of my friends has a form of OCD called false memory OCD -- or at least that's what he calls it, and what other patients call it -- where basically his mind will construct false memories of horrible things that he's never done. But the memories will seem so real that he will spend twenty-four hours a day, because he doesn't sleep much, obsessing about these false memories asking themselves, could they be true, could they not be true and then creating all kinds of mental rituals to try and make it better. Obviously, that leads to suicidal thoughts. It's just absolutely horrific. 


Another form of OCD is what they call post-natal OCD, just like you get postnatal depression. These will be new mums. They will just get an intrusive thought, “What if I suddenly threw my baby out the window?” And they'll be just like, “What a horrible thought to have. I must be an absolutely awful horrible person. I better never have that thought again.” And so then they're checking if they have that thought and obviously what you have is the pink elephant thing. And they're like, “I've had that thought again. I must be a really, really horrible person,” and then they start obsessing about it and trying to think positive thoughts. Then they don't dare touch their baby, and it just all escalates and it just gets totally out of hand. Just awful. 


So anyway, I was finding that treatments were pretty poor. It tends to be high doses of antidepressants -- sertraline, Prozac, etc. -- with all kinds of side effects. They take months to have an effect. Or there’s cognitive behavioral therapy, which also doesn't always work and which is very hard to access. In Cambridge, we have an eighteen-month waiting list to access cognitive behavioral therapy. So, when I got very bad six years ago, my older brother told me "Look, if you set up a foundation to fund research into treatments, I'll support you and help you get this off the ground.” So that's what he did. Orchard OCD, basically, we're entirely nonprofit and we fund noncommercial projects that will help develop treatments. We have two projects that we've really worked on. 


The first is a medical device called transcranial direct current stimulation, which is a small medical device where you put two electrodes on your scalp, and it puts a very thin nearly imperceptible electric current. We did that with Professor Naomi Fineberg at the University of Hertfordshire and it was a feasibility study. It detected a signal as in, patients saw a noticeable reduction in their obsessions, in their OCD. Now we're raising funds for a much larger trial to really test that. 


Then the second study, which starts any day, is testing a psychedelic. You're probably aware that psychedelics are the new frontier in neuroscience. People have known about it for decades, but because of the completely stupid drug laws that we have -- which have made them all completely illegal -- it's only recently that research has started. I mean, it's just criminal what these drug laws have prevented people from doing. But anyway, we are funding Professor David Nutt, who's a big name in this area at Imperial College, and we did a crowdfunding campaign for that. It will be an eighteen-month study on twenty patients where they will be given ten milligrams of psilocybin, which is the active ingredient in magic mushrooms. It’s not enough to have a full-blown psychedelic trip, but hopefully enough to help with what we call cognitive flexibility, which is the kind of rigidness in thinking which seems to be at the core of OCD. So yeah, that's why I'm involved in that. We just did another call for proposals and we should hear in the coming weeks who's the winner for that, and we'll be funding them. So, the idea is to develop new treatments for a very misunderstood and very under-researched mental disorder.


Shiv Gaglani: That's very exciting. One of our previous guests on the podcast was Jim Fadiman, who is the father of micro-dosing on psychedelics. My board member Mitch Rothschild, his wife, Rachel Yehuda, runs the Mount Sinai and Veterans Affairs MAPS trials for PTSD using MDMA assisted psychotherapy. So, it's a very exciting time. It would be very interesting to see which one of those, or hopefully both of them, have had an impact on OCD. You've done it before for AKU so I'm positive there'll be some good outcomes for OCD as well. 


I know we're coming up on time, and I want to be respectful of yours. I have two last questions. Osmosis is a teaching company at its heart. If you could snap your fingers and teach any group of people -- the public, health professionals, researchers, or anyone -- about something, what would it be and why?


Nick Sireau: Well, the first thing for rare diseases would be to help people understand that these rare diseases are common. When we did a survey a few years ago on students about rare diseases, we asked them how many rare diseases you think exist. The answer is generally "Oh, we reckon there might be five rare diseases affecting a few hundred people in the UK. " Actually, there are seven thousand rare diseases affecting millions of people. So, I think that's the first thing people need to understand: that rare is common. That's the key thing. 


Then on OCD, I think, for people to understand that OCD is a devastating disorder and to really help people to stop using this language which devalues OCD. It might seem like just a few words, but it has an impact on clinicians who don't take OCD seriously; it has an impact on funders who don't take OCD seriously, and hence, often don't want to fund OCD; and it has an impact on the pharma industry. I was speaking to some pharmaceutical investors the other day, and they were like, "Why would we want to invest in OCD? It's not a particularly nasty disorder." And I was like, “It is horrific and at its worst, it's as bad as full-blown schizophrenia.” So those are the two things I really want to focus on.


Shiv Gaglani: That's really, really helpful. We'll do our part on at least the first one. We're already starting to. The second one we can further explore. 


Then last question…what advice would you give to our audience about approaching their career in healthcare?


Nick Sireau: I would, gosh…that is a really interesting one. I'd say to keep a really open mind when you approach your studies. To look at what is not always the most obvious. I'd say that's the first thing. The clinicians and scientists that I've been really most in admiration of are those who have a very open mind, and who will go down areas that other people won't. I say that would be the first thing, 


Secondly, to really go to those areas that are under-researched and where there's a real underdog, which you get a lot in rare diseases. From a career perspective, it's not going to be amazing, really, for your career to particularly study a rare disease, but the impact that you can have on a population -- which is more or less abandoned by society, and by kind of the medical industry -- I think, is absolutely crucial. 


The third thing is to really be motivated. My hero is Professor Ranganath, who I've known for twenty years. Without him, none of what we've accomplished could have been done. The NHS in the UK is a pretty difficult environment to work in. I think it's getting more difficult for all kinds of reasons and yet people like Professor Ranganath are the real heroes who are driving things forward. He has 100% commitment to the patient, but also real curiosity in the science and I think that's what makes a huge difference. I always say when I speak to new rare disease patient groups, “Try and find your Professor Ranganath because that's what will make a difference.” I think he's the kind of example for new scientists and new clinicians who are entering the field.


Shiv Gaglani: That's amazing. I would argue to that, if you dedicate a summer, a year, a fellowship, or your career to a rare disease as a current or future healthcare professional, as you said, the patient groups are so happy and so grateful for that person taking their time. But it could also be career game-changing because, as we said, if you discover something, or develop a new protocol, or clinical trial or repurpose a drug, it could have a massive impact, right? Like, would these with these malaria trials be potentially happening without the AKU society digging that up and then happening to be at Liverpool? Maybe not and maybe...


Nick Sireau: I don't know, but what I do know is our AKU team in Liverpool is really collaborating with the guys at the Liverpool School for Tropical Diseases, so there are some real synergies there.


Shiv Gaglani: Well, Nick, this has been a total pleasure. Thank you so much for taking the time to be on the podcast, and more importantly for the work that you're doing not just for AKU and your family, but for OCD and rare disease in general.


Nick Sireau: Excellent. Thanks for your time. Good to speak to you.


Shiv Gaglani: And with that I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to Raise the Line and strengthen our healthcare system. We're all in this together. Take care.