Episode #4 ADOA podcast: Hedy about research into ADOA(-plus)

Below you will find the transcript of this podcast.

00:00:03 
Maud: Welcome to the ADOA Podcast. ADOA is a very rare hereditary eye condition. My name is Maud van Gerwen and I am here with… 

00:00:11 
Lion: Leon Augustijn. Together we will talk to professionals and experts about their view on ADOA. Welcome to this podcast. Well, welcome to this podcast. Next to me is Maud, and we interview Hedy about science. 

00:00:29 
Hedy: Yeah, that's an episode in itself I think, because there are so many developments going on in the world that we're involved in. It's just really great to be able to share that.  

00:00:46 
Lion: Yes, are you involved as a foundation like ADOA or are you also a bit of a driving force? 

00:00:52 
Hedy: On the one hand we are the driving force and on the other hand, I call that focal point, you are simply the spider in the web within the scientific research world, for researchers, for pharmaceutical companies, to bring together everything that has to do with ADOA. We have aspired to that role. I think that now, after six years, we can say that we have achieved that. 

00:01:23 
Lion: And what does that ultimately yield? 

00:01:28 
Hedy: A very concrete example, there is now a pharmaceutical company developing a drug, and to develop a drug you first have to do research. But at some point in all those phases that are there to bring a drug to the market, you need patients to test on. And right now we are busy finding those patients. So we inform patients that they are looking for patients to test the drug on, but also, that is what they call in English a natural history research, a natural progression, to see if something is effective. Then they have to look at: “How does it normally progress?” And if we use a drug, is the progression different? They need patients for that. And ADOA is of course a rare condition, so the search for patients is simply very difficult. It is now well organized in the Netherlands because we have a Dutch base. That is also starting to happen in other countries, but we do all that from the Netherlands. We reach patients all over the world from the Netherlands. That means that if a company comes from Australia and says: “We need Australian patients”, we try to approach those patients. And then they can continue. If they don't have patients, they can't develop anything. That's how it works. 

00:03:05 
Lion: And what other investigations are still ongoing? 

00:03:09 
Hedy: You have different types of research; you have fundamental research where they really look at the disease mechanism. So they want to understand very well why that optic nerve dies, what happens in those cells, the developments are enormous. In-depth knowledge is needed of what exactly goes wrong, at what level. And the further they get in terms of deepening what is possible in the human body and in such a cell, there is always a piece open where they cannot yet see exactly how it works. So fundamental research is about the disease mechanism, so "How does it work? Why does that optic nerve cell die? What happens with ADOA-Plus?" A lot has already been done in that, but there is still work to be done. And the moment you have that clear, you can say: "Okay, what are the possible solutions?" And then a whole new world opens up again, because in our case it is mitochondrial, in other words it is in the energy metabolism; the energy factories of the cells are defective in us, in people with ADOA. So that's one angle, mitochondrial, to either repair things there, or to exclude the harmful influences. Another angle is gene therapy, CRISPR-Cas, where you intervene directly in the DNA - because we are dealing with a hereditary condition, an error in the DNA, such as an OPA1 mutation. Yes, CRISPR-Cas, what are the possibilities there? Then you cut a piece of your DNA, and you replace it with a good piece, so that you change the DNA fixed. Well, that's one angle. You also have fundamental research into healing, where they regenerate optic nerve cells and the insulation layer that surrounds them. There are many conditions that affect the optic nerve. The best known of these is glaucoma, for example. A lot of research is being done into it, a lot of money is involved, because there are many patients. There are already treatments for it, but no cure yet. There are studies in the world into regenerating, regrowing, optic nerve cells. And what we try to do is to tie in with that, from: "What is causing our problem? What is the cause that we have? The mutation on the OPA1 gene?" And from there you cycle along, so to speak, to see: "How can I make those optic nerve cells grow again, without creating OPA1 again?" so to speak. The optic nerve cells are the most difficult cells in the body, the most complex. You scratch a skin cell open and it heals, but an optic nerve cell, if it's dead, it's dead, so to speak. The pharmaceutical companies are busy keeping those optic nerve cells alive, so to increase energy production. That's again with a technique called mRNA. It's a bit comparable to the Corona vaccinations. And they ensure that the energy production remains in order, so that the cell stays alive. It's very complex, you hear it, I'm also very enthusiastic about it. And that you as a patient, and in my case also as a mother, get everything involved in that, yes, I think that's very special. When I was sixteen, I also stood outside the ophthalmologist's office and said: "Well, you have ADOA and you can live to be a hundred with it, but I can't do anything for you anymore". That was the message. Then this is the extreme on the other side of course. 

00:07:47 
Lion: Yes, and those ongoing studies, do you publish them on your website? 

00:07:52 
Hedy: Yes, we have a series called: “The Road to Treatment”, and all the things I just mentioned come back in it. We have a volunteer, who is also a father, his name is Peter, and Peter is the one who organizes all of that for us. And the nice thing about that is, then we have Olivia, who lives in America, who also has ADOA, Chrisina lives in Germany, also has ADOA, Jonas lives in Sweden, also has ADOA, I am in the group, Kim, Ralph, and Peter, and we have a WhatsApp group together, and we all search the internet with everything that has to do with regenerating optic nerve cells, with OPA1 mutations, with ADOA. And we take turns with: “Have you seen this research? Have you seen that research? Have you seen this research?” So we share that information. Every one or two studies per month that come up there. Then Peter gets in touch, and in the beginning he got in touch and then we never heard anything again. But if we contact them now, they know that we also want to fund research. What helps? Or they are looking for patients. So everyone wants to talk to us and have a conversation with us. And the nice thing about that is that you can then share that with your supporters. As a point on the horizon, that is what we raise money for, but also just understand — we also have fellow sufferers who just really want to understand, or they have a medical background, and just want to understand what exactly is going on. That we then share that information with each other in that way, with all people with ADOA, but then also from Europe, America, all together, I think that is really nice. 

00:10:00 
Maud: Recently the foundation actually made a donation for a study? Can you tell us something about that study? What it focuses on? 

00:10:14 
Hedy: Yes. What I just mentioned a little bit, the optic nerve cells that they can grow back. That research, there is a worldwide consortium for that with all kinds of bigwigs all over the world who are working on solving that problem. So I have a damaged optic nerve cell, or a dying eye, and how can I make it grow back, that is a kind of saint's pleasure in that world. One of the chairmen of that consortium is the doctor at Stanford, Jeff Goldberg, and through Sander who already had contact with him we came into contact with them, and they are doing a very large study into the regeneration of those optic nerve cells and the insulation layer, because that also appears to be affected. That is already being financed from other sources and from other families with other conditions. And the donation that we made ensures that they will also specifically look at: "How does that process work with a cell that is affected with the OPA1 mutation, so an ADOA cell?" It is really fundamental, so it will be a long time before anything comes out of that. Millions are involved in that, to eventually get that done. But because all those doctors are working together, it is already such a large study, you can get a lot of value for your money for a relatively small amount, to put it in Dutch.  

00:12:07 
Maud: Exactly, so ADOA is simply included in a larger study, as it were, as an additional piece.  

00:12:12 
Hedy: Yes. 

00:12:13 
Maud: Well, nice! 

00:12:14 
Hedy: Yes, that's fantastic. That's impressive too. I was at EUNOS, the congress for European neuro-ophthalmologists, they are neurological ophthalmologists. And when you tell them that you're in talks with Stanford and with Jeff Goldberg, and that you're busy..., they all go: "Oh, that group is doing something, isn't it?" You know, I always think that's great, that they're making a difference there in that way. 

00:12:49 
Lion: Yes, and that is actually very special because it is a very small foundation of course. There are few people, because it is rare, who have that. So the patient group is also low. So how do you ensure that when you do research there you have a larger group of patients to do research on? 

00:13:13 
Hedy: They already thought of that when we founded it, which I wasn't there of course. With 500 people in the Netherlands, you can't make a dent in a pack of butter. But then we take those 2600 Germans, and then we take the Belgians and the French. It's a kind of franchise formula. We have people from almost every country in the world who have found us. For example, in Germany we already have someone who is in contact when a German patient reports, then they all call Christina, and she helps them on their way, because you also have country-specific problems. I believe we have the website in eight languages, we made the patient brochure in Dutch, then in English, then in German, it is now available in Italian, in Spanish, in French, it is still going to be in Swedish. And that's how you distribute it. We are now working on a healthcare provider brochure, so that will have to point out to doctors: "This is the clinical picture of people with ADOA". That will also be available in Dutch, and then in English, and in German… And that way you create a kind of oil slick where the Netherlands is the basis and you actually copy the rest, where the current technology is of course fantastic, because yes, translating doesn't have to be that difficult anymore. And we also get help from doctors in the Netherlands to get the content right, and we really think about that, about what we communicate. And having those patients under the button, so to speak, is interesting for researchers if they want to do research. One of the most recent developments is that in America, there is a sister organization called the ADOA Association, and they are a bit more focused on fundraising and raising money, so they are less of a patient organization like we have arranged here in Europe, but we work together with them. And they have, together with the organization Global Genes, for rare diseases, genetic diseases, they have ensured that there is an ADOA database, called Rare-X, that is now online. Patients can enter their own data there, and also determine their own data with whom they want to share what. And that's a start. That starts with one, two... but at the moment that all patients in the world, ideally, a bit visionary perhaps, but okay, enter their data there, and that data of course makes it valuable. Then you can also see: "What is going on with whom? What are the common denominators there?" You can do something with that. For the time being, it is only in English. But we are in talks with that organization to see: "How do we make that available in Dutch as well? And in German and in all other languages?" so that we can reach everyone. 

00:16:32 
Maud: Yes, exactly. Because I wanted to say: “Can we now also use all our data there?” Or do we have to wait until it is in Dutch?” 

00:16:44 
Hedy: You have to sign a legal contract for that, so you give permission. All those consent forms are in English, so you really have to be proficient in English to be able to give permission. And the questionnaires are all in English too. So you have to be proficient in English to really know what you are sharing and how you are sharing it so that the data is also reliable. 

00:17:07 
Maud: Yeah, exactly. So it's not just like, "Well, I'll give you my name and my address and I'm done."  

00:17:16 
Hedy: No, I had that hope too, but we happened to be talking to them this week. Then I thought: "Oh great, huh? I saw that the website was already in multiple languages", but that was indeed just the website and the plug-in for the website. But then again, there is much more to it with questionnaires that are under license. So it costs money to convert them to other languages 

00:17:38 
Maud: Yes. 

00:17:38 
Lion: Yes. 

00:17:39 
Hedy: But I keep holding on to that phenomenon of: “Six years ago there was nothing, just nothing”. And we are six years on the road and everything is profit, as in: “In the desert every plant that comes up is a bonus”. And with that input and with that energy, then it also remains fun to do and also beautiful to do. 

00:18:07 
Maud: Yes, a lot is really happening there at once. 

00:18:10 
Hedy: Yes. 

00:18:11 
Maud: Beautiful! 

00:18:11 
Hedy: Yes! 

00:18:14 
Lion: If I'm listening now, and I think, “Well, I really want to know something specific about this now,” how can people who investigate, or for example a contact person… 

00:18:30 
Hedy: There really is a lot on the website. Of course, we have a lot of people who are visually impaired, so reading a lot of large chunks of text doesn't make us happy. There is a ReadSpeaker on it, which reads aloud. Coincidentally, in the preparation for today, I thought: "Well, instead of staring at the screen in the car, I'll turn on that ReadSpeaker. So I just listened back to all those episodes that way. There is a lot of information in there.  

In France, they are working on mitochondria. They are working on a nutritional supplement to investigate with B3 nicotinamide. That is a path they are investigating of: “Well, could this be something that could help keep the cell healthy?” In Italy, they are also working on mitochondria, but then more focused on the active substances in idebenone, which is a medicine that is used for Leber's. Because we received a lot of questions about idebenone, Peter and Christina have written a whole piece about idebenone, including an explanation of how it works and why it might or might not work for ADOA. So all the pharmaceutical companies that are now working on a medicine, there are four of us in direct contact and we think along with them in the trials, in the questionnaires, in the test locations. For one of those companies, Amsterdam is now becoming a test location. It is of course fantastic that it is coming so close. A few years ago, we could not have dreamed that it would be like that at all. 

00:20:28 
Lion: And suppose I'm listening now and I say: “I hear a test location in Amsterdam, and I want to sign up…” Or is that too soon? 

00:20:35 
Hedy: At the moment there is a call on the website for one pharmaceutical company to register. That is also a whole process, clinical, from scientific research to medicines, how do you bring that to the market? That is also about clinical studies. Peter also wrote a whole article about that, so that is also on the website of “Op Weg Naar Behandeling”. At the moment you can register if you live in Australia for the actual testing of the medicine. If you live in the rest of Europe… in a number of countries you can register to participate in the 'Natural Course' study of that company. And then they will select people from those people or ask them to actually participate in testing the medicine. 

00:21:37 
Lion: And the website is…?  

00:21:38 
Hedy: adoa.eu . What is also important is the quality of life. Of course, this is all very much focused on a medicine, treatment, healing. Recognition of being visually impaired, the problems that come with it, the energy, the fatigue of simply going through life with much less vision and going through life with limitations, dealing with grief… In Amsterdam there is a department of the AMC, called: Low Vision Research, where various PhD candidates have done research into energy, but also into depression. There is now a study going on in which they are looking at – this is relevant for people with ADOA-Plus – “What is it like to live with a double disability?” So both poor vision and poor hearing. And what comes out of that are very practical things like a module that helps people with poor vision – so not just ADOA, but broader – to deal with depressive complaints, or to deal with energy burden, fatigue, to deal with that practically in order to become more resilient. Those kinds of themes. And that we, as a primarily Dutch patient organisation, are involved in these studies, are included, people come to our peer support days, we interview them for the website, in this way you also contribute to better care for people with poor eyesight and people with a combination of poor eyesight and hearing problems. 

00:23:38 
Maud: Yes, that is also very important. 

00:23:43 
Lion: Yes great, thank you! 

00:23:43 
Maud: Yes, thank you! 

00:23:44 
Hedy: Yes, you're welcome!  

00:23:48 
Lion: Thanks for listening to this podcast. 

00:23:51 
Maud: If you have any questions or would like to chat, please contact us via our website adoa.eu.