Daniel Lewi is the Founder and CEO of the Cure and Action for Tay-Sachs (CATS) Foundation, which supports children and adults affected by Tay-Sachs and Sandhoff disease. Daniel’s daughter, Amelie, was diagnosed with Tay-Sachs disease in 2011 at 15 months of age. Sadly, Amelie passed away in December 2017 at the age of 8. Lewi has continued to support and fight for other families with the condition, being heavily involved in ensuring patient involvement is at the forefront of clinical research.
Please note the transcript has been edited for brevity and clarity.
FLG: Hello, everyone, and hi, Dan. Thank you for joining me as we explore patient perspectives and look at the impact that genomics is having in patient care and lives. But before we do that, Dan, if you could just introduce himself and give us a little bit of background about what you do.
Dan: My name is Dan Lewi, and I am the co-founder of a rare disease charity for Tay-Sachs disease. The organisation is called the Cure and Action for Tay-Sachs (CATS) Foundation, and we support children and adults affected by Tay-Sachs and Sandhoff disease, both known together as GM2-Gangliosidosis. We were setup back in 2011 when my daughter Amelie was diagnosed with Tay-Sachs at 15 months of age.
FLG: For those who don’t know, would you be able to give a bit of a background of this disease?
Dan: In a really simplistic term, it’s a genetic disease where the mum and dad pass the gene on to the child, and they lack a certain enzyme in the brain which clears away waste products. Essentially, there’s nothing there recycling that waste, and then that builds up and causes a relentless deterioration of their physical capabilities and causes brain damage. Unfortunately, the kids go from appearing healthy and normal, achieving the milestones for many of them, then over time they lose the ability to walk, talk, crawl, feed and end up with uncontrollable seizures, dystonia and with feeding tubes. It is a very harsh disease that the children suffer from. There are three variants. The most severe form, called infantile, tends to come on very early on in life. Then there is juvenile, which becomes more apparent in teenagers, and then adult onset. The prognosis for all three variants is the same. You end up requiring 24-hour care.
FLG: Your daughter was diagnosed in 2011. What was your experience like getting that diagnosis?
Dan: I think the experience we had with Amelie really showed the postcode lottery because we’re based in London, so we are able to get a really quick diagnosis. This is how quick it was. Literally one day she just stopped walking and crawling. There was no reason, she was perfectly happy, but she just decided that she didn’t want to. We took her down to the GP and the GP was concerned thinking that there could be a brain tumour or something as there’s no reason for a child at that age just to stop doing certain things, like walking and crawling. We were referred to a local hospital in Lewisham, then went on to the Evelina Children’s Hospital where she was diagnosed with Tay-Sachs after two weeks. So, they were looking already very quickly for a metabolic disorder, of which Tay-Sachs is. Her blood was tested, our blood was tested, and we found out we were carriers of the mutation, and she was suffering from the disease.
In terms of diagnosis, it was really quick. For us as a family, it was good in the sense that we had this child who, for all intents and purposes, was perfectly happy and smiling, but we were explained at the time that the disease was severe, and she would probably end up passing away by the age of three or four and would require 24-hour care. As a parent, that is really difficult to fathom at that diagnosis moment because your child is sitting there happy, smiling and playing with toys and they were saying that she is going to have uncontrollable seizures, feeding tubes, you are going to need to get carers in to look after her. You think, ‘Wow, are we actually going to experience this, with this child sitting in front of us.’ But on the flipside, through the charity we have met families who have been through years and years finding a diagnosis and by the time they eventually get it, their child already has a feeding tube and is in a wheelchair. So, we do feel fortunate that we had that early diagnosis. We had a good nine to twelve months with her to be able to do new experiences and do a lot of things before the disease really was that severe and she required a lot more care.
FLG: At the time of diagnosis, what was known about the condition?
Dan: Tay-Sachs is quite a well-known disease. It was around 1881, I think, that it was first seen. It is normally diagnosed quite quickly on the back of a cherry red spot in the eye. So, it is actually one of the textbook ones they have in medical journals about genetic disease, and that’s kind of where it stops. A lot of people have heard of it, especially its higher prevalence in certain communities. But the disease itself, we’ve really seen an uplift, since the charity was started, of people understanding the prognosis of the disease and understanding the stages, understanding the process of what happens to someone affected. Because it was very common and we hear stories of families who were diagnosed in the 90s, that it was, ‘You are never going to meet another family. It’s so rare (it’s one of 320,000). Go home, enjoy your time together – your child is going to die’. And that is it. The information was very scarce. But what we see now, is that parents through the age of the Internet and social media have become much more aware of what the disease is doing to the individual and, actually, how they can do intervention to maintain a higher quality of life. And that’s the big shift we’ve seen, especially in last ten years, where parents are being empowered to take control of the care of the children affected by the disease.
FLG: What sort of tests were conducted to diagnose your daughter?
Dan: I think she went in on maybe a Tuesday or a Wednesday, and she was transferred over to Evelina from our local hospital in Lewisham because they didn’t have an MRI machine. So, we took her over and they did an MRI, and they found some white matter changes on the brain, and they did a few more tests. And I’ll never forget, it was on a Friday, and they said, ‘Look, we will send you down to this clinic (it was an ophthalmology clinic). We are going to look for something called a cherry red spot. It is purely just to rule a couple things out. It is not going to be a big issue. It’s non-invasive. It’s a Friday afternoon – we will get you in at the end of the clinic.’ So, we were sitting there, and I remember my dad going, ‘Fine if you go to that. I’ll head home and get a few more things for you guys (my wife, Patricia, and my mum). You take her down to that, and then I’ll come back in the evening.’
We went off to this clinic and we were literally added on at the very end, about 5:30pm, and they were like, ‘We have just got to test for this thing.’ They got the scope out; had a look and I’ll never forget. She was like, ‘Oh, just a minute, I just want to get a colleague.’ The colleague had a look and was like, ‘I just need to get the senior doctor in’. And he had a look and that’s when he said to us, ‘We have found something called a cherry red spot. This could be one of three or four diseases.’ We said, ‘How bad is it?’ And he said, ‘Well, if it’s bad, it’s terrible, the disease. And if it’s good, it is still going to be really bad.’ So, we went back to the ward, and they were like, ‘We thought we were going to rule certain things out. Unfortunately, it has ruled certain things in, but now we know what we can test for.’ There were like four different diseases they could then do the genetic testing for, which was to look for enzyme levels, which they did for Amelie, and that is how they discovered Tay-Sachs, and that was testing mutations. There’s lots of different types of mutations. I carry a very common mutation of the disease and my wife carries a very uncommon mutation, so they had to do a bit more work to find the underlying cause. That’s the process she went through. It was very quick. But again, it was that Friday afternoon, trying to rule something out but, actually, it ruled it in.
FLG: How much support were you and your wife given in regard to understanding the disease and its inheritance?
Dan: I have a background in science, so I understood genetics and inheritance and how it worked. So did my wife. So, we were kind of fully aware that it was something that we had passed onto her. This disease follows autosomal recessive inheritance, so we weren’t affected. We just happened to pass the mutation onto her. What was interesting was a few weeks/months later when we were then looking at the impact that it had on my wider family because they had children. It was a decision about who gets, do they get tested, why should they get tested. We noticed a lot of people chose not to get tested. My parents then got tested, to see who was the carrier. So did my wife’s parents. And then the ramifications are then different parts of the family being tested. Obviously for us, we would have more children, it’s then, they need to know that they’re carriers of the disease because you need to be prudent that if you know this disease is impacting your family, you don’t want them to be in the same position that we’ve been in, which is where you have a child affected by Tay-Sachs disease.
FLG: How difficult was it to have those conversations with the wider family?
Dan: It is really difficult because it’s that whole ‘it would never happen to us’ attitude. But when you are the family that is the one in a million, or one of 320,000, you struggle. And we struggled when some family members were like, ‘It’s fine, it will never happen to us’ and you’re like, ‘Well, you don’t know that.’ A lot of these sorts of diseases tend to stay in communities. I was born in Scotland to a Welsh mother and English father who has a Jewish background but had no idea about Tay-Sachs disease. My wife is Portuguese, she moved to London for university and ended up staying and we met just randomly one night. So, for us to meet, marry, have children – I mean the odds of that happening are very low and then to have a child with Tay-Sachs is even lower. So, it’s kind of making people aware that these things unfortunately do just happen, so if you know about it you should be getting tested because you can stop a lot of heartache and unnecessary pain that someone would go through.
FLG: You have two other children – what was your experience like knowing that they could potentially inherit the genetic variant? What sort of support did you receive?
Dan: That was a big one. We had lots of genetic counselling because we made a decision that we wanted Amelie to be a big sister. I think with our second daughter, Grace, the impact of going through the process of trying for children naturally – we made the decision that we didn’t want to go through pre-implantation. We wanted to try for children naturally and hoped that we had a good outcome, which fortunately we did. But I don’t think we fully appreciated the mental stress of that process of waiting for the test, CVS or amniocentesis, in my wife’s case. Then, with our son, who is our third child, it was much more stressful. I think because we went through it once before, we knew the whole process and it was just very stressful because you don’t know. Obviously, I am the father, so I don’t know what a mother is going through carrying a child. Not knowing whether it’s a child who is affected by disease and then having to then make another decision whether you keep it or you don’t. A lot of support comes from your genetic counsellors, who are talking you through the process, what to expect, what you can plan for and what you can’t control. But knowing that you have so many options, which I think is really good, that you’re not restricted to not being able to do things like IVF or pre-implantation or to try naturally. So, it was a very stressful time, but you get through it.
FLG: It is good that you have options and then you can decide yourself which path you want to go down and that they are there to support you.
Dan: When you get the results back, you just pick up the phone and they say, ‘Hi, it’s so and so from blah blah blah, we have the results. I’m just going to tell you them.’ They tell you straight away! So, you don’t have any moment of that awkward silence or ‘Oh, how are you?’ It’s, literally, these are the results, digest it, have a chat and then I’ll call you back in an hour and talk it through in more detail, which I think is really good because you don’t want to be left on the phone waiting for the results.
FLG: You said you have a background in science – what did you do prior to setting up the CATS Foundation?
Dan: My background was in psychology, so I did that at university and my master’s in Applied Psychology. Then, I moved into investment banking. That was my career up until the credit crunch. So, I was fortunate, when Amelie was born, where I was working, the bank ended up going and I was made redundant, but I was able to take a bit of time out. Amelie was actually diagnosed and born while I was having some time out. So, I had to manage that whole process of having a new baby, a new baby that was dying and then looking for work. Alongside my wife, what we decided to do was to set up the CATS Foundation because there was no kind of dedicated support from people affected by Tay-Sachs disease here in the UK. That was our focus – to make sure that people didn’t come out of their diagnosis being told they will never meet another family, go home, enjoy your time together and there’s nothing we can do. We wanted to change that experience for those people in the future.
FLG: What was the journey like setting up the CATS Foundation?
Dan: It’s hard work, but we had a very clear mission to provide support to families, to bring them together, to show that you aren’t alone and then start looking at ways we can impact research and impact the way that people look at the disease and can we actually get some clinical studies started in the disease – that was our main focus. But for us, it was very obvious that we weren’t really going to be able to do anything for Amelie. So, any research, any studies we were looking into, would never impact her. And I think that made things a little bit easier, we weren’t chasing that miracle cure for her, we were doing it for the wider community. So, we never felt that pressure, that time is ticking away with Amelie and unfortunately, we knew she was going to die from the disease. She lived a lot longer than we thought – she lived to the age of eight, when we were told three or four – so we feel blessed to have had that time with her. And on the side, we have been able to drive lots of research and quality care people get and build a community, which was sadly lacking here at the time.
FLG: What was it like having that community as a support network?
Dan: Huge! Huge, because it is people who know what you’re going through. They know the experiences; they know the late nights. When the kids have seizures, sometimes you might get a couple of hours sleep at night, things like that, knowing those challenges that you’re going through and sharing experiences. One of first big projects we did was developing an app that was based on videos and patient and parent testimonials about how they manage aspects of the disease and also family life. So, you can actually hear it from the horse’s mouth – you can share your experience and advice and I think that’s really important. At the time, social media was really booming, and people were connecting, and we wanted a way that people could actually advise each other on small little things and also the big things, like how you manage relationships in your family and with other family members, having more children, which we were talking about earlier, managing seizures and when you do feeding intervention, and all these big discussions you have.
FLG: What are the future plans or goals for the Foundation?
Dan: For us, the goal was to shut the charity down because we have treatments, newborn screening, early diagnosis – everything sorted. I believe we will get there at some point. But at the moment, our real focus is to get some symptomatic treatments out there. Since we set up in 2011, where there was no real research and no industry involvement, we’ve been able to drive forward a couple of gene therapy programmes which are now in the clinic. We have been able to get a drug repurposing study up and running, we have a couple more studies in the pipeline which will be starting in the next 12-20 months and a few more which other companies are working on. Getting that industry involvement has been really important because that raises awareness of the disease to the wider community, awareness of the disease to doctors and researchers, and that then gets more and more patients involved. That’s been really important to show. It’s a rare disease – we know that – but actually, we’re all working together all around the world. All the patients, all the patient groups are working together to drive forward this work, which is why we are seeing this kind of explosion of treatments potentially coming to the market in the next few years because we showed that there are patients there for people.
FLG: Last year the UK Government released the new rare disease framework. Do you think there is enough support for rare disease patients and groups?
Dan: No. But we never will, and we know that. That is why it is really important that we all work together on the mission. But I think the diagnosis is the beginning of that journey, but there is so much that happens before you even get there, and I think that’s where families need a lot more support. It is that whole process of how they get to that diagnosis, in the coordination of care, then access to medicines. Again, it’s that big issue of putting a price to life and, unfortunately, we are in a position where that does happen, where drugs become too expensive to get into children. I think it is weighing up how we can navigate that, because I really believe that, as more and more rare diseases are researched and treatments come to the market, we’re going to get more of these conversations happening. One thing that we have done at the CATS Foundation is to make sure we get those conversations going nice and early so we don’t run into roadblocks where companies may say, ‘We have this treatment, but no one will pay for it.’ We want to make sure that when they say this treatment works, we can get it straight in. And so, I think we need to do that collectively as patient groups and patients, to the lobby for better access to medicines. I think it’s a fight we are always going to have, and I can see it happening more and more and I think everyone needs to be more aware that this situation needs to stop.
FLG: I heard Stephen F. Kingsmore discuss how in the future, our discussions about the diagnostic odyssey will recede and we will begin to discuss the therapeutic odyssey. So, the time from once you get a diagnosis to actually treat the critically ill child. I think that’s going to be really important, especially in terms of access. It is heart-breaking to see people having to raise money just to get access to some of these therapies. What role do you think patient voice will play in helping to raise aware and getting people to take notice?
Dan: I’ve only been in this world 10 years now and I have really seen a big shift in the patient and patient group voice being more and more important. We’ve been invited to the FDA, the EMA, on boards with companies to advise on strategies and clinical trials on how they can do patient recruitment. I think that’s really important because anyone who is watching this who is a patient or patient carer will be told, ‘You will become the expert.’ That’s great, and we do. But you need to be listened to. So, if you’re telling us that we’re the expert, then give us due respect that we are the expert and what we’re saying does hold value. I think maybe 10-15 years ago, parents were just ignored, but more and more we are now being respected and we have that seat at the table to help in that decision process of how clinical studies can get going. I always say the biggest crime for me would be to have a trial that failed, not because the drug didn’t work, but because the clinical trial design was so bad. That involves choosing the right end points, making sure it actually has an impact on patient quality of life, and that’s where we, as advocates and also patients, can really make the biggest difference because we know the day to day of living with the disease. It’s not what you see in the clinic – it is actually what happens at home, when you’re cooking dinner, when the other kids need to be picked up from school. How is that child’s quality of life going to be improved on that treatment?
FLG: Patients are often only involved in research when it comes to human clinical trials. What is the importance of strengthening patient involvement in research, particularly in early-stage research?
Dan: That’s a really good question actually. What we’ve been trying to do is to get the companies involved as early as possible in the disease. I think everyone at a company who is working on a treatment in early stages should see the impact of the disease. It should never be, ‘We have this new drug for Tay-Sachs – come and tell us about it.’ And then everyone in the company, when they have this treatment ready to go, are like, ‘Oh, my God, I didn’t realise that’s actually what the disease does to the individual.’ Everyone needs to know that from day one when they start working on it. And getting involved in that process nice and early, and listening and understanding what’s important to the patient, what’s important to the patient carer, how we can get these things approved, what we should be looking at – that’s where we should be having these conversations really early. Companies need to be aware that we want what’s best for the community and so when we challenge them, we’re not challenging them because we don’t agree with what they’re doing. We are challenging them because we have the patients at heart.
FLG: What work have you been doing trying to do to ensure the ethics of clinical research has patient benefit at the forefront?
Dan: For us, it is making sure endpoint selection is correct. I mean there’s no point having something that is not going to have a meaningful impact on quality of life, and I think that is what should always be thought of when you are doing the trial design – how can I impact quality of life? And sometimes unfortunately, it is not extending length of life. With Amelie, from the age of 2, any treatment extending her life until she was 30 would have required 24-hour care the whole time. It is not being afraid to realise, actually, what do we tweak to make things easier? If we could stop them having seizures, that’s much better than making someone live longer. And making sure that we really understand the prognosis of the disease – how it impacts someone, and also the impact on the parent and carers and the wider family – and that needs to be really considered, especially in these sorts of paediatric diseases. The impact is huge on the family. And any treatment should also have an impact on that issue – it shouldn’t be adding burden to their life. It is the same with taking part in the study, it shouldn’t be bringing someone into the clinic every three weeks to give him a lumbar puncture. One, that’s cruel to do a lumbar puncture, and two, it’s actually really cruel on the parents and carers to be taking a sick child into hospital that frequently. Can we do things from the home setting? Can we do much more minimally invasive procedures as part of the study? Maybe the data you get won’t be as high quality as a lumbar puncture, but actually, you could be getting good quality data on the disease in the individual.
FLG: With the Foundation, you’re always having to communicate with scientists and with researchers. What has it been like for you trying to form those links? Have you found genuine support and interest from clinicians and scientists about researching the disease?
Dan: For sure! I think for us, one of the big things we did was to actually just raise awareness in that community – not in the wider public, but in the research and pharma industry. Giving talks about the disease, being receptive to their involvement and not being portrayed as a difficult group to work with. For us, it has always been really collaborative, and so any companies’ interest in GM2, Tay-Sachs or Sandhoff, we speak to them, we work with them, and we advise them. I think it’s really important to have that collaborative approach because, at the end of the day, they want to get a treatment and we want the treatment. Let’s work together! That’s how we look at it and I think that is how we have seen the success of being able to go to meetings and represent the patient. We are not there to understand the biochemistry of the disease. That’s not our role. Our role is to represent the patient. I think that is really important, and we’ve been really clear in that whole process in where we stand. We are not there to be intellectually sparring about enzyme levels and things like that. That’s not our role. Our role is about the patient.
FLG: How can we as a community bring in patient voices? What would an ideal scenario look like?
Dan: I think in terms of the rare disease space, what I would really like to see more of is basket trials. So, bringing together similar diseases with one potential drug or therapy that you could do for multiple diseases at the same time. I think that approach gets you more patient numbers. I think it’s easier to get approved that way and you can impact more people. By working together as patient groups, you can then learn from each other, and you can help each other move forward that process, not just for that one treatment, but for other treatments going forward. I really believe that we should start looking wider because more and more rare diseases are being diagnosed all the time and more patient groups are starting. I am involved with Findacure mentoring network, and more and more groups are starting, and they are on the same journey we were on 10 years ago. It’s really exciting, but they’re going to get to where we are at some point, which is how do you get these treatments, how do you interact with pharma, how do you get them into the patient and how do you get them approved. I think working together collectively as patient groups with pharma is the real key because we all want the same thing, which is to get these to market.
FLG: What would you say to someone who is just starting up a patient group?
Dan: It is a hell of a ride. Back yourself, trust your judgement and be collaborative. I think that is the real key – and listen to other people. Because one of the successes we had was leveraging the expertise of those around us, and so we’ve been able to drive forward a lot of work because we’re willing to work with different people. We don’t sit there and say, ‘We are the be all and end all. We know everything about the disease and about clinical trials.’ We bring in people when we need them to support us on certain tasks, and that’s how we have driven forward a lot of our work. I think it’s being happy and willing to do that and being collaborative is so important. And like I said, it’s a lot of work – not for the faint-hearted!
FLG: How has the pandemic impacted the Foundation and the rare disease community as a whole?
Dan: Unfortunately, we have seen some families really struggle. Not through access to any services, but actually realising that this is a year of their child’s life that they should be making memories, that they have not been able to. That has been really difficult for us as a community to see, and we’re not the only rare disease community that has seen this. It has taken away this opportunity of getting out and doing things with the kids as and when you can, and so we’ve all had to be a lot more resilient and understanding that the community needs to work together to provide that level of support. So, we have done a lot of work, like check-ins with families, peer matching them up so they have support networks which are closer and can help them through difficult times, and just making sure that everyone can still make those magical times together. Because, unfortunately, there’s no beating around the bush, the kids die very young with more severe forms of disease, so it is about making sure that the life they have is as high quality as possible.
FLG: Do many families stay a part of the community after their children pass away?
Dan: I think that’s actually one of the biggest successes we have had, is that people get involved in the charity when their children are affected but they stay involved with us all the way through. So, when we hold our annual conferences, I think we now have more people who are bereaved attending than those with children who are still living. And I think it is a testament to the community feel – that they feel part of something, that they can really feel at ease and share their experiences. I think it’s really important that even families who have been bereaved for many years still feel they can come to these events and feel part of something. And that’s what we always say to people: this isn’t just a community for now, it is a community forever – just come and join!
FLG: Thank you so much for joining me today, Dan. The work you not only do for the CATS Foundation but also the wider rare disease community is amazing, and I hope the rare disease community continues to get that support and are able express their voices within research. Thank you so much for joining me today, it’s been great!
Dan: Thank you, Shannon.