Bowel Research UK CEO Kathryn Pretzel-Shiels is joined by members of the AMELIE project team to discuss this groundbreaking research. AMELIE (Anchored Muscle cells for Incontinence) aims to help people with faecal incontinence due to anal sphincter injury, particularly women who have experienced this injury through childbirth. In this clinical trial, muscle cells are attached to microcarriers and implanted as part of regenerative cell therapy to restore muscle function. Professor Richard Day, Professor Charlie Knowles, and Dr Marina Yiasemidou discuss their roles, the progress and challenges of this research so far, and the potential benefits to patients in the future.
Find out more about the AMELIE project
Follow AMELIE on X: @amelieproject, and on Instagram and Threads: @amelie.project.eu
Music is “Summer Guitar” by Amaksi from Pixabay.
Transcript
Sam Alexandra Rose
Welcome to Can I Butt In, the Bowel Research UK podcast, where we welcome bowel cancer and bowel disease patients, researchers, healthcare professionals and carers to butt in and share their experiences. We’re picking a topic every episode and getting to the bottom of it.
Kathryn Pretzel-Shiels
Well, welcome everybody. I’d like to introduce a fascinating project, AMELIE, which is short for Anchored Muscle Cells for Incontinence. This is a five-year collaborative research project funded by the European Union Framework Program. It involves a collaboration of 13 organisations across nine countries to develop and carry out research. The project has been co-ordinated by UCL and led by Richard Day, Professor of Regenerative Medicine Technology at University College London. My name is Kathryn Pretzel-Shields. I’m CEO at Bowel Research UK, and it’s an honour to be with three guests today to talk us through this fascinating project. Our guests are Professor Richard Day, Professor Charlie Knowles, and Dr. Marina Yiasemidou. I’d like to start by welcoming all three of you. And Richard, tell us how you got involved in AMELIE.
Richard Day
Thank you, Kathryn. I’m a scientist based in the Division of Medicine, and I’ve always worked at the clinical scientific lab interface, working for many years in gastrointestinal research. And whilst looking at various disease types over the years, we’ve been trying to make models of diseases in the lab to try and replicate the tissues in the body. And we realised quite early on that in order to make cells grow like tissues in the lab, we need to provide them with the right environment. Now this initial research took place probably 10, 15, even 20 years ago. If you jump forward to now where we’re at today in modern medicine, people are trying to deliver cells into the body to regenerate tissues. But if you don’t give those cells the right environment when you’re delivering them, they won’t survive, they won’t thrive and they won’t regenerate the tissues that we’re trying to target. So this led to an idea that I discussed with Charlie about how we could try and improve some of the therapies that were being tested to try and make them better, to try and make the cells survive and regenerate tissues and hopefully improve tissue functions in the body. And in this case, for the AMELIE project, we’re focusing on a muscle that controls continence. So that was really the initial starting point of the AMELIE project.
Kathryn Pretzel-Shiels
Well, terrific. Thank you. And you referred to Charlie. Charlie, how did you get involved?
Charlie Knowles
Well, I’ve known Richard for some time and I mean, Richard, as he’s alluded to, is the brains of the operation. And I’m the surgeon, really the chief clinical investigator of the AMELIE project. So I’m responsible for delivering the trial. Richard and I, guess, yeah, it probably goes back 10 years, the inception of this study and talking about the principles of it, as he’s outlined. But the idea that the anal sphincter, one of the most important muscles in the body when you think about it, I mean, there are a few small muscles in the body like the vocal cords and the sphincters that fulfil absolutely critical functions either to life or your social functioning. And things go wrong with these muscles. And we’ve had regenerative medicine, huge area of study, one of the big areas of modern medicine where there’s been a colossal expansion in new technologies. And we wanted to apply some of those new technologies to this difficult problem of faecal incontinence to try and regenerate the anal sphincter in the AMELIE project, notably in women who have suffered anal sphincter injuries as a consequence of childbirth, which is a very, very important group. So my role has really been to, with Richard, to deliver the AMELIE study. I’m an honorary professor at University College London and professor of surgery at Queen Mary University London. And I work at Barts Health and the Cleveland Clinic. I’ll stop there for now.
Kathryn Pretzel-Shiels
Thank you. And Marina, certainly not least last here. Tell us about your involvement.
Marina Yiasemidou
So I am a colorectal surgeon. I’m a consulting colorectal surgeon at the Royal London, which is part of Bart’s Health and Queen Mary University, where Professor Knowles is a professor of surgery. I’m at the forefront of functional bowel problems where I receive patients in my clinic and I understand the major problem and impact on their quality of life from having a sphincter injury during childbirth. So I’m involved with recruiting patients. But overall, I’m involved with treating patients with fecal incontinence on a daily basis and understanding the major impact on their daily lives and the stigma that sometimes it carries or the embarrassment that they have. So I’m quite keen to be involved in research that will enable us to find new treatments for them to help them improve their quality of life.
Kathryn Pretzel-Shiels
Perfect. Well, thank you to all three of you. Richard, this is an incredible project looking at all the countries that were involved and all the institutions that are involved as well. What happened that got you to lead to this project coming together? Was there a moment that you realised that something needed to change to improve the treatments and the therapies that were available?
Richard Day
Yes, basically. To enable this type of project to move forward and to be translated into the clinic, it’s a truly multidisciplinary project. So we need lots of different organisations with different types of expertise to be able to take an idea from the lab all the way through the non-clinical testing, through the regulatory approval process, through the contractual complexities of working with multiple institutions and then being able to deploy this in the clinic where people like Marina and Charlie can hopefully deliver this into patients to be able to test whether initially whether it’s safe, but hopefully in the future whether it actually has a beneficial effect. So to be able to do that, we recognised that we needed multiple partners; one organisation couldn’t do it all by itself. So it’s bringing together a group of experts, in this case from across Europe, with different levels of, different areas of background expertise, which then combine and over time address the different challenges that are faced and then in this case, succeeding to get it into clinic and into patients.
Kathryn Pretzel-Shiels
Being able to bring all of that together at the start, I don’t know if that’s a normal process to happen. Charlie, can you talk a little bit about how widespread this problem is and is that a normal process to be able to bring all those teams together at the beginning?
Charlie Knowles
Yeah, so faecal incontinence, I think it’s worth for the audience, giving a bit of background here, is not an uncommon problem. So if you look at population surveys where you send out by post or by email a survey about leakage symptoms of faecal material, you will find across multiple Western countries a population prevalence of about 9%. So 9 out of 100 people suffer some degree of faecal leakage. And this is obviously, the proportion of people who suffer this is polarised by factors such as age, so very much more common in older people and particularly common in people in nursing homes and with other medical disorders. And obviously that 9%, almost one in 10 people don’t suffer the sort of faecal incontinence degree that we’re talking about in the AMELIE study. So many people would manage this at home or just live with a small amount of leakage or get products from the pharmacy, etc. But if you look at that, probably one in ten of that group, so one in 100 overall, have faecal incontinence to a level of severity that would bring them to a specialist to seek more advanced treatments. And probably of that one in 100, half of those, so we’re now down to 0.5%, would be into the realms of failing the first line of treatments that are available for faecal incontinence. So things like medicines like Imodium, devices to wash the rectum out, enemas, other first line treatments, continence advice, dietary changes, lifestyle changes. And that group of patients, which we’re still at one in 200 of the population here, and this group are more common in women by probably 10 to 1 compared with men, are a problem when it comes to treatment because we don’t have great treatments for that group. And in fact, we haven’t had any new treatments for that group in 30 years. So the mainstay of treatments in the past have been things like sphincter repairs, which are not free of problems and of complications and are only suitable for a proportion of patients in the first place. Sacral neuromodulation, which is a stimulated way of electrically stimulating the nerves that go to the lower bowel and the sphincters. That is a helpful therapy, but it doesn’t treat everyone and it’s not suitable in everyone. So there’s this unmet clinical need in this area and a desperate need for people to be trying to, as we are, to bring in new treatments. And to perhaps close the circle on this, the idea of using cells into the anal sphincter is not entirely new. And indeed, I was involved in a trial between Canada and the UK in the past using cells. But as Professor Day has alluded to already, there are problems that require people like him, cell biologists and other partners who are involved in the basic sciences to think, how do you keep those cells alive when they go in and in the best condition to have the effects that you want them to have, which is both to rejuvenate the environment around them, but also to engraft in the existing older, less functional muscle that’s there. And really that’s what AMELIE is and anchoring these cells to the microcarriers that are used. I’m sure Richard could talk more on that, on the actual technology. But this is the inventive step in this, if you like, and the shift, hopefully, when we have clinical data that may change, which cells on their own may not work, probably don’t justify the cost and logistical challenges of them. But together with the microcarriers, we’re aiming in AMELIE to see if that changes that. And I mean, to come back to the point you asked me about and Richard alluded to, growing cells of itself is not difficult. Growing cells and sticking them to microcarriers is not difficult, but doing that in a regulated environment where those cells have to come from a real human individual and go back safely into that human individual is a massive challenge. And that’s the five years of work that’s really led up to this. I’ll hand over to maybe Richard, do you want to add something to that?
Richard Day
Sure. I mean, the microcarriers or the materials that Charlie mentioned that we’re growing the muscle cells on, they’ve been under development for many years prior to the AMELIE project starting. And actually, Charlie and myself worked on a previous clinical study where we were looking at the equivalent material, but for repair of another condition associated with the GI tract called fistulas. So, we initially took those materials into humans for the first time in that study. And actually, as a consequence of that study, when we were looking at how those materials behaved with cells when we were exploring them in the laboratory, we recognised that these materials provide a very good surface for cells to attach to. And that meant that we had a material that essentially, we could deliver cells into the patient, into the body in a more natural anchored state. And that’s really important as Charlie’s alluded to because muscle cells in particular are very sensitive to being detached and left in a suspension, floating around. So, if you grow cells in a conventional way in the laboratory, that’s fine. They thrive and grow. But as soon as you lift them off that surface to be able to, in this case, inject them back into the patient, those cells, the majority of them die within a few days. And that obviously has a negative effect if you’re injecting them into a patient and you’re wanting those cells to restore muscle function. So, the materials that what we call microcarriers that we’re using, they’re very small beads of a polymer that degrades in the body. So, the polymer is made of the same material that’s used for dissolvable sutures and stitches that have been used for many years in a clinical setting. So we know that the material is safe, but the idea is that in the form of a very small microsphere or microcarrier, these can be of a size that’s injectable, so it will go through a syringe and a needle, but we can grow cells on the surface of these little microcarriers and then inject the cells whilst they’re attached to the microcarriers into the patient, thereby providing a more natural environment for the cells to be delivered in.
Kathryn Pretzel-Shiels
Wow. And it sounds so microscopic, you know, so small. It’s not something you can see what you’re doing all the time. Is that right?
Richard Day
Yes. So, the actual size of the microcarriers, they’re about the size of a grain of salt. So you can just about see them. Obviously, you can’t see the cells on the surface of the microcarriers with the naked eye, but when you look under the microscope you can see that the cells provide a covering on the surface of the microcarriers and they attach and they spread out before they’re delivered back into the patient. So these, should be said, are cells that have been derived initially from the patient. So the patients have a biopsy, so a small piece of tissue taken from a muscle and those pieces of muscle are digested in the laboratory. When I say digested, they’re broken down into the individual cells. Those individual cells are the cells that are then attached to the surface of the microcarriers, which can then be delivered back into a different site in the body. So in this case, the sphincter muscle. thereby hopefully providing new muscle tissue for the area that’s been damaged.
Kathryn Pretzel-Shiels
Wow. Charlie, does that get to the point that the clinicians get involved yet or is that too early for that?
Charlie Knowles
I mean, I was just going to add that when the cells come out by biopsy, and I will hand over, I think, to Marina. Marina’s done the biopsies here and she’s injected the cells and we can go to her to get her views of how that’s gone and what’s involved, is to say that these cells are, we’re not just injecting the cells that we took out back in. These cells are expanded by some very clever processes in laboratories into millions of cells. So in big flasks, if you like, and then those cells filtered out of the flask. And there are a number of other processes, including NHS, the blood transfusion service at the NHS, who do the final step, which is to attach them to the microcarriers in a process that is regulated, as I’ve said, so that these can go back in. And those processes had to be created. I mean, that’s a big stage of this is to create, validate, confirmed the safety of and the regulation in this area is not light and quite rightly because injecting cells, much like giving a blood transfusion, can be hazardous if you had the wrong cells, infections, a number of other things. So there’s a great deal of process. But maybe Marina, you could give us, you’ve, we’ll talk a bit about the biopsy. and the experience of patients and then how you’ve seen these microcarriers floating around in syringes and going through the needle and maybe tell us what that’s like.
Marina Yiasemidou
Yeah, thank you. Thank you, Prof. So essentially, what’s really impressive about this trial, because I have been the principal investigator for other trials, is how much our patients want to participate. I mean, I still see patients in clinic that have heard about this trial. And I have to say, unfortunately, we closed recruitment, which is a good thing to keep in mind for AMELIE too. So for me, the process is fairly straightforward in regards to the clinical things that had to be done. So our patients would come in for a biopsy of the muscle that lies right behind the breast tissue. And that happens under local anaesthetic with about a 2-centimetre incision. And that’s how we harvest the muscle. Then we send it off for someone else to do all the difficult work for us, our scientists. And then we receive it back for the patient to have the aid injections under ultrasound guidance, which is one of the major differences of AMELIE compared to other trials that have been done before. So it’s done under ultrasound guidance. And that’s again a day procedure where our patients will come in the morning and leave in the afternoon. And in terms of, I think Prof Knowles has touched upon this, that we have several treatments. However, they have variable success rates at the moment. And for me as a clinician, the good thing about AMELIE is that it’s relatively minimally invasive. It doesn’t entail having a permanent implant like the sacral nerve modulator or other forms of neuromodulation that require the patient to come in for several sessions throughout the week, which can interrupt with their daily activities. So there’s definitely a need for a more successful minimally invasive treatment that we are hoping to achieve with AMELIE.
Kathryn Pretzel-Shiels
Wow, that’s a fascinating process that’s happened, and I can see why you certainly needed three different areas that you all represent, but also all of the others as well. So Richard, take us back. You have this idea, you have some of the science to back it up, and then you want it to become an AMELIE project with all the right funding and all of the participation from the different countries and different organizations. How do you start on something like that?
Richard Day
So it’s a fairly complicated framework of different partners involved in different aspects of the project. So we needed to engage with those partners very early on during the planning of the project to make sure that we were talking to the right people with the right capabilities and the right know-how in terms of being able to take this forward for what we wanted to try and achieve. So we knew that we had to not just deal with the science, we needed to work out how we were going to take the technology forward and test it and in terms of pre-clinical testing. So in order to get regulatory approval, we needed to conduct pre-clinical testing or non-clinical testing. So again, they’re all different areas of expertise that we needed to bring into the project. On top of that, in terms of the funding requirements for this particular project, there was a need for good public dissemination and that’s where we were able to work with Bowel Research UK, which has been a fantastic partner on the project in terms of disseminating the project. On top of that, there was a component of the project whereby we needed to plan for the future. So there’s what we call a business development work package, where we’re looking at how this technology that’s being conducted at the moment at a very small scale can be expanded and scaled up to make it so that the technology can be used for the wider population. So in order to be able to do that, there needs to be a business plan of how we take this technology forward, ultimately commercialise it because we can’t continue to take it forward in a university setting that to be able to get it out to the wider public. We need more funding, we need a bigger organisation to be able to help that happen. So we need to be thinking in the future, if you like, at a very early stage to be able to plan for this, not really knowing at the time what all the challenges would be. We could predict some of the challenges, but obviously there’ve been lots of other unforeseen challenges that have impacted the project and has required a certain degree of variation or adjustments as we’ve progressed. So that’s taken a long time to be able to get to where we are. It’s a very novel technology. So as I’ve said, we couldn’t really predict some of the challenges or unforeseen challenges at the time of writing the project proposal. But we’ve been able to overcome most of those and to be able to get to where we are today.
Kathryn Pretzel-Shiels
Well, and looking at the start date, it was 2020 and there was something else that was going on at that time. How did COVID impact the work that you were doing?
Richard Day
It had a big impact. Supply chains, as for everyone else, were impacted, access to laboratories. So at the time, it was early in the project, we were doing more of the laboratory non-clinical research and that had a very big impact in terms of how we could progress some of those work packages early on in the project. We also had Brexit or the impact of Brexit to deal with, which again wasn’t trivial in terms of a European funded project. That again created some challenges, shall we say, particularly in terms of regulatory approval. So we had to get regulatory approval both in the UK and in the European Union, whereas previously it was harmonised. So it would have been one regulatory approval process. We had two approval processes to go through and to be able to move the investigational product from the UK into the European Union there were additional issues or challenges with customs clearance and things like that, which again, when we were planning the project, we couldn’t really foresee that being as big a problem as potentially it has been. And that has had an impact.
Kathryn Pretzel-Shiels
Well, being mission-led in what you were doing is helpful because you still think with the solution in mind and what will happen. Marina, can you take us through that? You talked about the process of what will happen with a patient. What’s next? When do they start to see or feel a difference and what treatment do they require after that?
Marina Yiasemidou
So essentially, we had some unofficial feedback from our patients. So we do keep in close contact with, just to make sure that there were no obviously adverse events from procedure and also to see if they’ve seen some improvement in their symptoms. And what we’re hearing is very encouraging. They can already see that there is some improvement in their symptoms in terms of the amount of time they have issues with faecal incontinence. I mean, there are objective measures through the studies protocol that we monitor and we will continue to monitor that. But the unofficial feedback that we have is that they’re already seeing some improvement in their symptoms, which is really encouraging.
Kathryn Pretzel-Shiels
Fantastic. And Charlie, what about from your perspective?
Charlie Knowles
Yeah, I mean, I think it’s important for the listeners to realise that the AMELIE study in its current form is primarily directed at demonstrating safety of this new technology and technique. And it’s great that we’re hearing some favourable results that may indicate efficacy as well, but we mustn’t get ahead of ourselves, and it will require a larger trial with a slightly different design to really prove that this treatment is effective and to what degree it’s effective in the future. And I mean, I’m sure the team, I know Richard’s already been working on this and brought me in a bit is looking now to getting the funding and the resources together to deliver that trial following on from the existing AMELIE study because I think it’ll be very important because at least in we’ve done five patients so far and there don’t seem to be any safety concerns to date.
Kathryn Pretzel-Shiels
Right. And Marina, you mentioned that there were other patients that have that heard about this so far. Where has the information been traveling through? I presume it’s more than just person to person. This information is getting widespread attention.
Marina Yiasemidou
Yeah, I mean, there is a lot of enthusiasm and our colleagues have been very nice to us. They frequently present AMELIE even if they’re not directly involved. Some of our patients have heard in presentations that there is this study; that is at the time was currently recruiting. Unfortunately, by the time I’ve seen the patients in my clinic, recruitment has stopped. But we do see posts on professional websites as well as social media about the AMELIE trial. And I think that the more we talk about it, the more we would be able to recruit or increase the curiosity of our patients. What is really important to say is that for myself, and I believe that in other centres, we are a tertiary referral centre for faecal incontinence, which means that we receive patients that have had other treatments that were not successful or not as successful as the patients would have liked in other centres. So they are patients that are very, very keen to try something new that will help them with their symptoms. And I think at times maybe faecal incontinence, because I do both faecal incontinence and cancer, at times faecal incontinence doesn’t get the attention that perhaps other conditions get. And that has been reflected widely in the amount of research funding that faecal incontinence conditions have been receiving, which may not have been as generous as things like cancer, for example. But it may not be as we would define life-threatening, but the impact and the chronicity of the symptoms on the quality of life or even their daily lives. We are talking about patients that can’t leave their home. So, I mean, it’s something to consider. And even if the one of the strongest messages that we put out there today is that we need to look a little bit more into investing into treatments for this condition because it has an impact on the individual, but also society as a whole.
Kathryn Pretzel-Shiels
Most definitely. I mean, when you look at social impact and if someone can’t hold a job, can’t take care of their family, can’t be part of their community in itself. It’s extremely challenging for them. And can you bring that to life for us? Can you talk about a patient experience of what you’ve seen?
Marina Yiasemidou
So essentially, we know from reports that have been done with, including Bowel Research UK, that we have many, many patients that wait for about ten years from the moment they originally build up the strength to go to their GP to report that they have a faecal incontinence problem. So most of our patients would come and say that it is quite embarrassing for them to even admit. And the figures that Prof Knowles quoted before, I believe they’re largely underreported because not many people can work up the strength to actually go to their GP and say “I have a faecal incontinence problem”. It comes with stigma, embarrassment, and when they do work up the strength to seek help, at times we can see, and it’s been reported in our clinics most of the times, that their symptoms are sometimes trivialised or not taken as seriously as having a problem that might indicate that you have bowel cancer, for example. So it’s extremely difficult to understand the magnitude of the problem because it’s underreported, but also is very difficult for the patients once they report their symptoms to actually get to the treatment, the appropriate treatment that they need to have.
Kathryn Pretzel-Shiels
Charlie, has this been your experience too?
Charlie Knowles
Yes, well I was involved with the All-Party Parliamentary Group for Continence, and a document that outlined exactly what Marina’s been saying. I mean, the pathway for patients with continence problems is broken in the UK and it’s a postcode lottery where it may, ten years might even be good to make it to someone who can actually understand and treat the condition. It’s a terrible problem, not restricted to the UK, in fact. I mean, it’s a problem through many countries. And the adage that it’s a disease that doesn’t kill you, but it ruins your life, is what we often say. And to add to what’s been said, I mean, I think women listening to this would identify with the issue, and I hear it in clinic all the time, that if you’re in a supermarket wearing a white pair of trousers and you have frank faecal incontinence, that isn’t just embarrassing, it’s traumatic. And it is something that you will never forget. And so once that happens a few times, this is a life shattering event where really we need more investment. We just need to do better. All of us need to be doing better. That’s not just new treatments; it’s investment in pathways and signposting people. as Marina said, to actually find the care that is available if you can really find it, which isn’t easy. So those are just some additional reflections really on the problem at the moment.
Kathryn Pretzel-Shiels
So Richard, this is terribly exciting where you are at the moment. What is the vision for the future? What’s funding look like? What more needs to happen in these early-stage procedures that have happened and the responses from the patients? What can we look to next and how can we all support it?
Richard Day
So the next step would be to make sure that what we’re doing at the moment is safe. And as we’ve heard, signs so far are very encouraging. We have a twelve month follow up period for each of the participants in the current study to ensure that the investigation or the investigation product is safe. In the meantime, whilst that’s happening, we are confident that we will get that safety readout. So we’re planning ahead to try and conduct a bigger study, which would involve more sites or more centres, more patients, have a comparator to demonstrate that what we’re doing does have a benefit over either existing treatments or a suitable comparator. That would be, as I said, a larger number of participants. We’ve got clinical sites ready to go for this. We’ve got regulatory approval ready for this. So we are actively looking at how we can maintain the momentum of the current project to move forward as quickly as possible. We don’t want to have a big pause in time before we can continue with this research. We’ve got everything in place, we’re ready to go. We just need to have the funding essentially to enable that to happen.
Kathryn Pretzel-Shiels
Is this information going global? Because again, as Charlie had said, this isn’t just the UK, it’s not just Europe. This happens around the world. Have you been hearing from scientists and clinicians globally who want to get involved and help?
Richard Day
Yes, and also from patients. So we’ve conducted some surveys which were open and we had patients from, or people affected, from around the world that were very interested in being participants in a future study. Unfortunately, as Marina said, the current study is closed to recruitment, but there isn’t a shortage of people that want to participate to try and help to move this forward.
Kathryn Pretzel-Shiels
Charlie, has that been your experience too?
Charlie Knowles
Yeah, I mean, call out to Marina’s team at Bart’s Health NHS Trust, but also to Cardiff and Julie Cornish and the other people have recruited in the current study. But also, we’ve got to thank the other European partners who actually had patients lined up, you know, for this study. Denmark, Spain, Austria, France. There were many patients who were looking forward to participating in this study and it is very unfortunate as Richard has said that Brexit and COVID and a number of other things have really slowed the progress of the current study to a point where that’s been limited to the UK. But we’re optimistic that we can move forwards with this if we can get the funding and it is a difficult funding environment at the moment to get the funding for studies like this. Marina said priority is often given to other things and disease areas even within the bowel, like cancer. But we have the willingness of these great centres around Europe, ready to go if we can get that funding and more centres in the UK as well. So we’re working on that.
Kathryn Pretzel-Shiels
Right. So if we were to look five years’ time from now, Richard, and we’re having this conversation, what would you tell me is different then from now if everything works in our favour?
Richard Day
So the whole project has been a steep learning curve, and we are continuing to learn as we go along in terms of the current clinical study. I think in five years’ time, we’ll be in a much stronger position if we are conducting further clinical studies whereby we have an investigational product that is almost an off the shelf type product. So we’re not constrained by the manufacturing timelines and the clinical scheduling, which currently can create issues with scheduling of the actual investigation at the moment. So if we have a product that can be stored frozen, then it’s available for when the patient can be scheduled for the clinic. And that will make life a lot easier. We should be able to manufacture more products in that way in a shorter period of time, which in theory should save money in terms of manufacturing costs. So I think there are things that we’ve learnt throughout the current AMELIE project where we can potentially create further improvements to make it easier to use for both the manufacturing perspective, but also from the clinical implementation of it as well.
Kathryn Pretzel-Shiels
Wow. So in ten years’ time, where do we hope to be?
Richard Day
Ten years’ time, it’d be nice to think that this was being implemented around the world. We would obviously need to think about how that is scaled up in terms of the manufacturing, the business model that would fall under. We need to have a sustainable process and manufacturing process and business to support this. But with encouraging results, that should fall into place because as Charlie mentioned, there haven’t been very many successful treatments that have come onto the market in the past 30 years. So there is an opportunity there. But more importantly, we want a treatment that works for the patients and actually restores and improves the function of this part of the body that will have a drastic effect on improving these person’s quality of life.
Charlie Knowles
Worth adding there, isn’t it, Richard, that as far as to our knowledge, this is the first example of attaching skeletal muscle cells to an anchoring particle like this anywhere in the body. So I mean, this may not just have reference to the treatment of faecal incontinence as we go forwards as well.
Kathryn Pretzel-Shiels
Yeah, no, I was going to ask exactly that, because many times you find that one thing has now impacted advancements in science and other areas. Can you assess where that might be or is it too early to predict?
Richard Day
Well, there are conditions that affect the GI tract. I mentioned fistulas earlier. So that’s one of the areas where Charlie and I are thinking about how we could deploy the same or similar technology, but with a different cell type to try and improve the healing of fistulas, particularly those associated with Crohn’s disease, but away from the GI tract. There are lots of other indications around the body where people are starting to think about using cells to treat the condition. But again, those cells like to be anchored to a surface to survive. So they need to be delivered in a natural anchored state in order for the therapy to be successful. So AMELIE really provides a foundation upon which we can potentially create a platform technology that could be applied to lots of different conditions and improve therapies for a wide range of people.
Charlie Knowles
I mean, an example there would be the heart, Kathryn. So when someone has a heart attack, part of the muscle of the heart dies and the people have started to explore the potential of using cell therapies to regenerate heart muscle. So that’s an example. But there are other muscular disorders, muscle injuries, etc. So yeah, it could be far reaching.
Kathryn Pretzel-Shiels
So then we think about the funders and the collaboration in doing that. I don’t know that there’s an amount to say this is what we need next to take this through, but how can listeners and others help to support on the funding front? Where do you go for the funding and how can we all help with that?
Richard Day
So in the UK, there are typical routes of funding that take a technology like this from the laboratory into the clinic initially and then beyond that to become a more industrialised product. So we’re talking about what used to be called the Research Councils or UKRI now and Innovate UK, for example, which takes things forward for commercialisation in the UK. Going back to the point that Marina made, you know, this type of condition isn’t widely disseminated publicly. There are conditions, other diseases, heart disease, cancer, that people talk about a lot and there are substantial fundraising organisations that support those types of conditions. This type of condition isn’t widely discussed, even though it affects a lot of people. So, you know, there’s a need, I think, for people to lobby some of those funding organisations to make sure that people are aware of how significant this condition is, that there are new technologies coming through that need to be supported to be able to demonstrate that they are beneficial. Otherwise, we can’t take, we fall into what’s commonly known as the valley of death, which, you’ve got a pretty good idea, but you can’t ever realise that and take it forward into the future.
Charlie Knowles
I mean, I think to answer your question more directly, and maybe Richard would disagree with me, but a million pounds would get us a long way. And with the competition to get such money from the councils, we’ll be perfectly open to philanthropic donations of anyone interested in this, other charitable foundations. And we will be looking at industry and whether they and venture capital. I think all of those routes should be considered.
Kathryn Pretzel-Shiels
Terrific. Well, you have a big supporter here, and I know that all of us at Bowel Research UK have been absolutely thrilled to be a part of this project. And it’s an honour to speak to all of you about the progress that has been made in spite of all of the issues that were mentioned before, least of all co-ordinating with all these different organizations and across all of these different countries. You’ve all become professional project managers, no doubt. So where does it go from here in terms of the structure and organization, if I can ask that question before we start to come to a close?
Richard Day
So AMELIE will exist beyond the current project. So the current project, as I’ve said, finishes in August next year, August 2027, which is when we have the twelve month follow up of the current participants ending. Beyond that, there is still a general enthusiasm amongst the consortium, so the different partners from across Europe to continue and push this forward. So as I said before, we want to maintain that momentum and that goodwill to ensure that we can take this forward. And the different partners are looking at, how they can support the technology going forward from their own respective countries as well. So we are we’re actively looking far and wide to see how we can take this forward.
Charlie Knowles
Short answer, Kathryn. We’re keeping the team together and we’re not going to lose heart. We will continue.
Kathryn Pretzel-Shiels
Yeah, it’s probably not a new space that you know that you need to wait until you see that the safety is there, that the results that you’re looking for are coming through. And that’s, you’re all very patient in that space, but it’s nice to see that it’s the duck whose feet are continuing to go in the water and keep things going while that’s happening so nothing stops. So if someone does want to get involved, if they want to help to support on the funding or the pathways, what’s the best way for them to get involved?
Richard Day
So we have a website, an AMELIE website, and on there is contact details about how you can either contact the organisation, Bowel Research UK in particular, to be able to participate or to provide opinions, thoughts, and just to learn about where we are with the project, because we’re providing regular updates in terms of how things are progressing. So that’s probably the best route.
Kathryn Pretzel-Shiels
Great, and we’ll include that in the show notes so that we’re able to share that through too. So, Marina, what would success look like to you on the AMELIE project as this is looking to come to a close in August of next year, what would the definition of success be for you?
Marina Yiasemidou
So essentially, there are two ways to look at it, in my opinion. One would be the research aspect of things, which would show a second larger trial, perhaps with a comparator, as Prof. Knowles explained. But for me, the most important thing, because I interact with patients every day, is if we have the future possibility of developing a successful treatment that will provide improvement in the symptoms and quality of life. We call improvement now or a success for the existing treatments if, for example, the faecal incontinence episodes reduce by 50%. So I am hoping that with new treatments, we’ll be able to do something better for us because we wouldn’t necessarily accept an improvement of 50% for other conditions, but we are accepting it for faecal incontinence. So success for me would be to provide something that is minimally invasive, that it doesn’t interrupt massively with providing a treatment doesn’t interrupt massively with the daily activities of a patient, but also provides an improvement of their symptoms that is perhaps way above 50% and what we accept for other conditions.
Kathryn Pretzel-Shiels
Right. Charlie, how about you?
Charlie Knowles
Yeah, I mean, I don’t disagree with anything that Marina has said. I think more specifically for a treatment like this, which is, even with all the scaling and logistics challenges overcome, this is never going to be a cheap and straightforward treatment. I mean, it will always be, it is a cell therapy and it’s an advanced treatment. And so what we really need to see is we need to at least see that a proportion of the people we treat with it are cured. We don’t want everyone to be a bit better. That doesn’t help anyone. What we need to see is that, and hopefully we can then define the group of patients who would benefit most from this and then be able to target this therapy in a precise way, what we call personalised medicine, directed towards that group of women or other patient groups that can really benefit from this in a meaningful way, as Marina said. And I think that’s what success looks like. And that would place this treatment firmly in the armamentarium, this rather limited armamentarium that we currently have as colorectal surgeons for helping people with this condition.
Kathryn Pretzel-Shiels
Thank you. And Richard, I’ll come to you with the same question, but also to think about what is it that you want the listeners to take away from today’s podcast?
Richard Day
There is hope in terms of a new therapy for this type of condition. It’s a fairly radical type of treatment in terms of it hasn’t ever been looked at before for any other type of condition. So we’re not taking an existing treatment and trying to adapt it and develop it for faecal incontinence. We’ve developed this treatment specifically for faecal incontinence. We’re optimistic that it will work, but to be sure of that, as I’ve said, we need the bigger study to be able to demonstrate that. But if it works in the way that we think it will, it will be transformative and hopefully benefit a lot of people.
Kathryn Pretzel-Shiels
What a legacy for all of you and for the project team overall. And it does sound like there are other project teams that can learn from the AMELIE project. What would be your three takeaways for them, any project teams that are working on something as impactful as the AMELIE project?
Richard Day
Probably perseverance in terms of if you’ve got an idea, develop it, talk to people outside. In terms of my expertise, I’m a scientist. So talk to people outside of your discipline or your own area of interest, get their opinions, think outside the box.
Kathryn Pretzel-Shiels
Great. Any final thoughts from Marina, you, Charlie, Richard?
Marina Yiasemidou
I would say that I wasn’t involved from the beginning of the project, but I can see how much work and how much perseverance, would be the word, was applied to reach to the point where I could and my colleagues administer this treatment to our patients. So I completely agree with what Richard has said.
Kathryn Pretzel-Shiels
Charlie, we’ll give you the last word.
Charlie Knowles
I just want to thank everyone who’s turned this podcast on and listened to it. I hope whether that’s a person who’s suffering with this condition or someone who’s just interested in the science and medicine of it, I hope we’ve generated some interest. So that’s great.
Kathryn Pretzel-Shiels
Terrific. And I will give a shout out for the website address because it will be in the show notes, but it is www.amelie, which is AMELIE-project.eu. So that’s AMELIE-project.eu. Thank you so much, Richard, Charlie, for your perseverance from the very, very beginning and having fantastic clinicians such as Marina to be able to bring it to life and see the face of the patients as they go through this treatment. We’ll all be watching closely to see how these five patients continue to progress and look forward to seeing more information on your website, press releases, more podcasts as well, so that we can thank everyone who’s been involved from a funding standpoint to the different countries and the different organisations. It’s been a stellar project from at this point in time, knowing that there’s been a huge amount of issues to have to deal through as you have discussed them, but we’re hoping for a very, very sunny future. And most of all for those patients and for those who will never have to experience what current patients have to experience now. So thank you very much for joining us and thank you very much for all the work that you’re doing and will continue to do. And goodbye to all. Thank you.
Richard Day
Thank you. Bye-bye.
Sam Alexandra Rose
Thank you for listening to Can I Butt In? This podcast was brought to you by Bowel Research UK. Find out more about the charity, our work and how you can get involved. Visit bowelresearchuk.org where you can join our People and Research Together network or PaRT, read about our research campaigns and fundraising, or make a donation to support the vital work we do. Let’s end bowel cancer and bowel disease.