How science and big data are helping in the search for an effective treatment of a rare disease that causes blindness – transcript

Ideas to Innovation - Season Two


Lissa Poincenot: Back in 2008, I really had almost no experience with legal blindness. And when my son started losing vision, first in one eye, and then in the other, I was absolutely terrified. The future that I saw for him looked bleak and I was scared for him, frightened, devastated, just did not know how to ensure that he would live a great life given this unusual situation.
Shyama Ghosh: Most inherited rare diseases, they show a birth prevalence. The condition develops soon after birth or in a couple of years. But with LHON, there’s a slight difference. So more research is needed into this as this may go beyond lifestyle choices as risk factors.

Intro: Ideas to Innovation from Clarivate.

Neville Hobson: Imagine that one day as you waited to catch your train to work or log into your Teams or Zoom account in your home office, you became aware that you’d suddenly lost your central vision in one eye. There’s no pain or sensation you could still see with that eye, but what you saw was blurry. Over the next few weeks, your other eye also loses its central vision. Each eye quickly gets worse as the central blurry blind spot in each eye, known as scotoma, rapidly expands over the following eight months or so.
These are the classic indicators of Leber’s hereditary optic neuropathy, LHON, a genetic condition affecting the optic nerve which is responsible for sending visual information from the eye to the brain. It’s a rare hereditary disease that affects young men mostly. In most cases, severe vision loss in both eyes is the outcome. While you can still see, you are typically beyond the threshold for legal blindness. Some treatments and lifestyle adjustments may help slow down the progression of the disease or improve vision in some cases, but it is life changing. Currently there is a lack of effective treatments.
Hello and welcome to Season 2 of Ideas to Innovation, a podcast from Clarivate with information and insights from conversations that explore how innovation spurs incredible outcomes by passionate people in many areas of science, business, academia, sport and more. I’m Neville Hobson.
It’s estimated that about 35,000 people worldwide have LHON vision. Put that in context, in November 2022, the United Nations estimated that the world’s population had reached 8 billion people. Yet while the number of people with this challenging disease may be low, the impact on them and those close to them is high.
I’m delighted to welcome two special guests to this episode to explore the effects and challenges of this rare disease on patients and their families and to help us understand the role and work of scientific research in seeking answers.
Our first guest who can speak from direct experience is Lissa Poincenot who joins us from Carlsbad, California. Lissa is the mother of a son who became affected by LHON in 2008 when he was 19 years old, and a daughter who was affected in 2018 at age 26. Today, Lissa is focused on supporting and developing the LHON community. Welcome Lissa, thank you for joining us.

Lissa Poincenot: Thank you for having me.

Neville Hobson: Our second guest is Shyama Ghosh, a senior principal content editor at Clarivate based in Antwerp, Belgium. She has a strong interest in rare diseases and advocates for relevant reporting to increase awareness about such conditions. During the COVID-19 pandemic in 2020, Shyama was part of a team of Clarivate epidemiologists who created a COVID-19 medical dashboard to help vaccine manufacturers harness the large volume of information emerging from various sources. Hi Shyama, thanks for joining us.

Shyama Ghosh: I’m happy to be here, Neville.

Neville Hobson: So I’d like to start our conversation with you, Lissa. You set up, a website through which you share what you learned as you struggle to cope with this disease and what you’ve learned over the years since it first happened, all part of helping to make the adjustment process smoother for others. You’re also deeply involved with a discussion group on Facebook that today has more than 5,000 members who share information about living with LHON.
Can you tell us about your experiences? I’m keen to hear also your thoughts about the lack of effective treatment in spite of much research over the years into LHON. What needs to happen do you think?

Lissa Poincenot: Back in 2008, I really had had almost no experience with legal blindness. And when my son started losing vision, first in one eye, and then in the other, I was absolutely terrified. The future that I saw for him looked bleak and I was scared for him, frightened, devastated, just did not know how to ensure that he would live a great life given this unusual situation. And I had two other teenage children at the time and when I learned that LHON was genetic and I had passed the same mutation to the two of them and they were at risk, I was worried about them also, but it also made me highly motivated.
I was really motivated to insure that Jeremy would be able to live a great life and I was motivated to make sure there would be a cure, a treatment, something that would ensure that should it happen again to one of my other children or if my daughter were to have children and she would pass it to them that there would be something that would change the outcome for her. I was super motivated to make sure that they would be protected and even I’m at risk and I’ve had to realize that I was looking for something for myself also.
So I started looking for positive role models, people who were coping well with LHON that could help guide me in this unusual journey. And I found people who were living positive successful lives with LHON and sort of followed their path and introduced my son to them. And that made a world of difference.
I quickly learned that LHON was much better done as a team sport, with people who understand this unusual condition and working to solve it together was much better than facing it alone. So that by the time my daughter became affected 10 years later, I was able to introduce her to so many people who were living with LHON, who were very successful, who had learned assistive technology approaches, and that just made life better.
So I’ve just been really working hard to make sure that everyone who’s affected by this can live successfully and move forward in a positive manner.
In terms of the research, I’m realistic about the research situation. LHON is a rare disease and we’re fortunate. We’ve really attracted quite a bit of interest in research. We’ve had clinical trials in a variety of modalities. And the problem hasn’t been solved yet, but people are working on it. And I think one of the problems is we’re such a rare disease that having the data sets large enough to figure things out has been hard to do.
So we’re working to build community, bring people together to make it easier for researchers to go forward with larger data sets.

Neville Hobson: That’s really an excellent foundation you’ve presented to us, Lissa. I mean, from your perspective as someone directly involved with someone who has this condition, and that’s really excellent what you’ve shared with us today.
So the question coming to my mind of course is to say, so what’s science doing to find an effective treatment and how is big data helping in that? And to help us understand what’s happening, I’d like to ask Shyama for her expert views from a scientific research perspective.
First though, let me ask you this, Shyama, I know you have a deep interest in the use of digital technology for improved procedure rates in medicine and one of your hobbies is metaphysics, I read. Can you tell our listeners about your interests and actually about your role at Clarivate?

Shyama Ghosh: Neville, I’m a molecular biologist and I have research experience in infectious diseases and vaccine development. In Belgium, I’ve served as past president of the Belgian Society of Parasitology. And in that context, I studied neglected tropical diseases and I’ve taught parasitology in African universities. I’m currently based in Belgium and I have a strong interest in rare diseases, especially LHON.
At Clarivate I serve as a science editor for the Incidence and Prevalence database. This database provides epidemiology and market research data and it enables life science companies to develop healthcare products and services. Moreover, there are current trends in artificial intelligence which indicate how we can use AI as a tool in life sciences.
So I’m very interested to study that and I also want to see and research how AI can make a positive difference in the lives of individual patients.

Neville Hobson: Okay, that’s a great introduction. On LHON and its current lack of effective treatments, we heard Lissa tell us about her experiences supporting her son and daughter and the impact of this disease. And indeed, Lisa’s comment, I think which feeds into our conversation that there is clearly a lack of effective treatments.
And I’m wondering how you see the current situation from the perspective of understanding a rare disease like this. We have the incidence and prevalence database in Cortellis as part of Clarivate, as you mentioned, that provides information on LHON, prevalence and primary mutations, morbidity and mortality rates.
Do we know enough though? It seems clear from Lissa’s experiences that we probably don’t, or indeed definitely don’t I would say. So is the real world data you have available enough, and is it good enough when combined or harmonized with published data?

Shyama Ghosh: Neville, companies do face challenges in developing treatments for rare diseases. So, because there are so many questions here, we need to understand what the patient population looks like, how do we identify such patients for clinical trial inclusion, and what are the treatment progression pathways.
Now, what we know about LHON is that this condition is frequent among teens and young adult males. However gender by itself does not influence the exact timing of the initial visual loss. So the question remains, why is it so?
Most inherited rare diseases, they show a birth prevalence. So the condition develops soon after birth or in a couple of years. But with LHON, there’s a slight difference. So more research is needed into this as this may go beyond lifestyle choices as risk factors. So in this context, real world evidence can be helpful because we’re studying a rare disease here.
So real-world evidence actually refers to data which is collected from everyday healthcare settings and such data can provide very important insights into different patient populations and also give us an idea how we can improve patient outcomes.

Neville Hobson: Okay, so you’ve given us an introduction there and thanks for explaining what real world data means. That I think is a key thing. So it’s from everyday healthcare settings, I think is how you’ve explained that.
Tell us a bit more about the actual information this will provide for you. You’ve given us an idea, but what else can you tell us about the further information that real world data can give you?

Shyama Ghosh: So real world evidence can identify previously undetected cases. So it improves the diagnostic rates because you’re following up on a very daily basis the condition of the patients. And real world evidence can also help to monitor treatment outcomes.
So what is required is that researchers interested in real world data, they collaborate and they prepare standardized protocols to collect this kind of data. And that can help to give a better understanding of that particular disease, rare disease, in this case LHON. So what we know from LHON that an accurate diagnosis is crucial for treatment.
So what we have done at Clarivate is that we triangulated several data assets like real-world data, published studies, clinical trial results, brought them all together to get a better understanding of this condition and what were the current drug uses for this disease. Moreover, real world data can also help us understand morbidity concepts developing from LHON. So what are the possible connections of LHON to possible movement disorders or other neurologic pathologies?

Neville Hobson: Okay, that’s most interesting. And Lissa, I wonder what you could add to that. What’s your perspective on what we heard Shyama explaining there?

Lissa Poincenot: My perspective is that the LHON community has been really fortunate. I’ve interacted with many rare disease communities since I got involved with LHON. And in many cases, people report that the researchers and the clinicians don’t feel warmly towards the patients, don’t collaborate very well. And for some reason, we’re just very fortunate in the world of LHON.
The clinicians and researchers have been very open and willing and eager to be engaged with the patient community. And our community is super interested in sharing data and learnings and information that can be helpful in the research and the researchers have been very interested in hearing what we have to say.
So it’s been very exciting to see how these collaborations have moved things forward. And I’m optimistic that we can continue to do more because there is so much more work to be done together.

Neville Hobson: That makes sense. Thank you. Shyama, you mentioned about the what the real world data can help you learn further and that age and gender can predict visual failure, I think too.
But predicting the onset of a rare disease like LHON and other rare diseases too, I would imagine, remains a big challenge, does it not?

Shyama Ghosh: Yes. So real world data and published results from literature, they have provided consistent information on LHON prevalence and risk. Having said that, an accurate forecast of disease onset in LHON carriers remains a challenge. So real world evidence has helped us better understand what the criteria for disease onset are.
So what we found was that the LHON prevalence varied between countries and regions. Real world data showed a 1.3 fold increase in LHON prevalence for the period of about four years between 2018 and 2021. Real world data also showed a high prevalence in non-Hispanic whites and that majority of LHON patients during that period were being treated with antibiotics.
So there are lots of questions here and uncertainties. It is unclear how many patients are currently receiving gene therapy for LHON, even be it on compassionate grounds. So given the promising clinical trials with gene therapy, the market potential is bright. However, this therapy has a narrow window of usage after symptom onset, because there is this period of months to about a year before there is complete loss of central vision. So real-world data, in this context, real-world data can complement ongoing clinical studies and help us get better information.
Another thing is artificial intelligence. So the mutation profile in LHON patients affects spontaneous visual recovery. So it has been reported in literature that patients with the ND6 mutation tend to have a less severe disease progression, which is not the case for those with ND4 or ND1 mutations.
So here, artificial intelligence can be used to screen databases to identify these specific mutation carriers. And so there are possibilities of combining AI and real-world evidence in the study of this condition. So these are some of the thoughts. And in the same context, we also propose continued research on stem cells to find more evidence whether this therapy can actually work in LHON patients.

Neville Hobson: That’s most interesting. I get the feeling that we’re kind of on the cusp of something that may well take us down that path that Lissa is concerned about in particular, on knowing more to be able to travel that journey towards a cure or more effective treatment. The AI element perhaps, given the attention artificial intelligence is currently getting in so many areas brings us to a point, I think, it’s a very good segue to this if you like, that we could look ahead a little and consider what the picture could be in 2033.
You mentioned there are some promising experimental treatments for LHON in various pipelines. And now we’ve got this, I guess, quite exciting potential, even from a lay listener’s perspective on the combination of artificial intelligence and real-world data combined. How can that work? You mentioned perhaps analyzing vast amounts of data is a good role for an AI tool to do that, speed up that research process, if you will.
So I guess the obvious question to start this part of our conversation is, what do you think we’re going to see in 10 years from now in terms of awareness of this rare disease, understanding of its consequences further and potential treatment? And of course, the big question, is a cure on any horizon anywhere?

Shyama Ghosh: Yes, Neville, overall I’m optimistic. In recent years, we have seen an increase in awareness and better diagnosis of rare diseases, which has led to improved access to care for patients.
Where LHON is concerned, the gene therapy, GSO10, is set to be launched next year in the U.S. And it’s already being provided on compassionate grounds in several European countries. Given the narrow treatment window, it is very important that LHON diagnosis rates are high and are kept high so that patients can access this gene therapy.
So I’m hopeful that many patients will be treated with this, with GSO10, and that this brings a lot of promise for the future.
And finally, I would like to say that as an advocate for raising awareness for rare diseases, I do advocate that genetic testing be available for all patients who meet the clinical criteria for LHON and who are at risk of sudden onset legal blindness.

Neville Hobson: Okay, so Lisa, hearing Shyama’s views there and looking ahead to this big picture in 10 years from now, what do you think? What are we likely to see? Or indeed, what’s your expectation?

Lissa Poincenot: I have a few thoughts on that, Neville. I think, first of all, LHON is a great disease to study, because if you think about it, generally people who are affected by LHON, we’re healthy. We don’t see very well if we’re affected, but we’re healthy. And people, as Shyama mentioned, are often affected in their teens and twenties, which means they have a long lifespan ahead of them and are available to be studied, can travel to a clinical trial site to be studied, which makes just a great group to be studied, and we’re motivated to find a cure. So I think we’re worth studying.
I think we understand as a community that being research-ready is important to researchers. So we’re working hard to create data sets about ourselves that will make it easier for researchers to learn about us and help them help us find those treatments and cures that we all want so so deeply. I think that it’s also important to point out that on the one hand we need and want an effective therapeutic immediately.
However, while y’all are working on that, we’re also working on making sure that everybody who is in this community can live a great life and does live a great life. We’re super fortunate that there’s lots of tools and techniques available, assistive technology and so forth, that can make life better. And so by having that information spread within our community, it makes people actually more willing to share the information with their maternal relatives that they might be at risk and they can then learn about how they can reduce their risk of onset.
So having a supportive community is really important. So overall I’m optimistic that the researchers can help us get to a solution and in the meantime we can make sure that anyone who does join our community by finding out that they have LHON, we can help them live a very good and successful and happy life.

Neville Hobson: That’s terrific. A very optimistic view, Lissa, that’s really quite something given the circumstances that leads to that optimistic outlook. Thank you for that view to 2033.
I actually want to ask you, Shyama, a final word on this in light of our conversation today, and particularly Lissa’s optimism about how people who are affected by LHON today can actually live an extremely happy and fulfilling life. Final thoughts from you on the research perspective on this 10 year out view? Anything to add to that?

Shyama Ghosh: I do believe that with the onset of GSO10 therapy, starting next year, to begin with, at least 10% of patients affected with LHON will have immediate treatment. So that’s already a very positive outlook and that will increase over the years.
So from the Clarivate point of view, our focus has been on the timing of the symptom onset and ensuring clinical effects. So we will continue to do our research into this and we will take the use of real world evidence to help us answer such questions like, a young man may be affected at age 20 or at age 30, what regulates this difference?
So there is a lot of research that is still necessary to be ongoing and we will be busy with that. And we hope to give the correct answers to the at large LHON community and to Lissa in particular.

Neville Hobson: That’s terrific. That’s great, thank you. So both of you, Shyama and Lissa, it’s been a great pleasure speaking with you both today. Thank you for sharing your experiences and insights on such a significant topic. Thank you.

Lissa Poincenot: Thank you.

Shyama Ghosh: Thank you.

Neville Hobson: For information about LHON, visit And for information on Clarivate’s work in real-world data analysis for life sciences and healthcare, search online for “Clarivate real-world data”. Ideas to Innovation continues with our next episode in a few weeks’ time. Visit for information. Thanks for listening.

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