Naji Gehchan: Hello, leaders of the world. Welcome to “Spread Love in Organizations”, a podcast for purpose-driven healthcare leaders, striving to make life better around the world by leading their teams with genuine care, servant leadership, and love.
I am Naji, your host for this special episode in partnership with Boston Biotechnology Summit, a bridge to collaboration and innovative synergies between healthcare stakeholders. Matthias Lambert a Senior Scientist in the division of Genetics and Genomics at Boston Children’s Hospital, and Instructor in the department of Pediatrics at Harvard Medical School. Matthias identifies as a patient-scientist, navigating life with a rare congenital myopathy. His research focuses on studying the mechanisms that contribute to the pathogenesis of rare muscle diseases including his own genetic condition. He is actively engaged in pioneering efforts to advance cutting-edge therapies for these conditions. His work is supported by prestigious grants from the National Institutes of Health, the Muscular Dystrophy Association (MDA), and the AFM-Telethon. In 2024, Matthias plans to establish his own independent research group.
Matthias, it is great to have you with me today!
Matthias Lambert: Thank you. It’s a great pleasure to be here as well.
Naji Gehchan: Before we dig in drug discovery and development, your passion and your focus during the summit, I would love first to learn more about your story and how you became this incredible leader and pioneer in research.
Matthias Lambert: So I was born in France. So I’m from France. Um, I went to science school. pretty quickly. So, um, after graduating from high school, um, I went to university in Lille. So it’s in the north of France. Um, I did a bachelor, master and a PhD, uh, on science, uh, and said physiology. And I was studying the muscle, uh, skeletal muscle.
And then I went for a postdoc. I went to Boston in, uh, 2017. Uh, I joined the lab of, uh, Luke Anker. Who discover the gene for, uh, the dystrophy in the, in the eighties. Uh, and so I’m working on different neuromuscular disease such as muscular dystrophy or, uh, al Myopathy. But more about my story, I would say I was a, a patient before being a scientist because I was born with a, a Lin Myopathy, which is a very rare, uh, neuromuscular disease.
Um, and so for 25 25 years of my life, we didn’t, we didn’t know the genetic cause of this is because I was the only one in my family, um, with this disease, very rare symptoms. And so when I was, uh, doing my PhD in France, I also had my physician in the same lab. Uh, so basically my physician became my colleague at the same time.
And at some point, you know, I was, you know, when I was studying the skeletal muscle, I, I, I went through, different papers that describe my symptoms for rare conditions. So I told my physician, you know, we should look at this gene. And basically what we did is, uh, took a blood sample and three months later the results came back.
And basically say that the gene that we were looking at was, uh, the good one. Uh, so it’s, this gene is called TPM3. And, uh, right now, I have established my, also my own research direction in the lab here in Boston. After my PhD, also working right now. on this DPM3 gene. And this is basically the, the basis of my future lab.
So yeah, this is my, my story.
Naji Gehchan: Wow. Thanks for sharing, uh, Matthias. And it’s, uh, it’s great advancement from discovering the gene to now opening a lab. Hopefully you can, uh, target that. So we’re going to talk about this. Uh, and I’d love first to get your high level perspective on drug discovery from a patient scientist.
As you would describe yourself, um, how is it different? And how do you think about drug discovery?
Matthias Lambert: I mean, this is different because we are not only scientists. Uh, basically the discovery that we’re gonna, we’re gonna make, they’re gonna be for patients, but also for us. Um, and so that’s the perspective is, and the, I mean, the perspective is very different because you wake up every morning and you say, maybe the discovery, the discovery that I’m going to make today, it is going to change my life.
Uh, in, uh, like, uh, health, uh, health wise. So, this is very, very important. That’s, I would say, the first, the first thing. Uh, and then, the, the, the drug discovery, uh, area, I think, right now, maybe, a little bit overlooked because we have a lot of gene therapy right now in the market, you know, we have CRISPR and I think it’s also a good time to, to, to recenter also our focus on genetic discovery because we have maybe more than 10, 000 FDA approved drugs that, for example, were not tested in my disease.
And so basically we have maybe drugs on the shelves that have maybe an effect on rare disease. So as those compounds, we know the toxicity of those compounds. We know that they are safe. Uh, they are already being done some development of those drugs. And so it would be very easy to, uh, repurpose, uh, those drugs to, to another condition.
Naji Gehchan: So as you were talking about it, you, you spoke about CRISPR, you spoke about probably screening the drugs that already exist. We know the talks about them and are they effective? Can I ask what are you most excited about from a technology standpoint that you think will literally change and accelerate drug discovery, uh, of, of this specific CPM3 gene, uh, and myopathy, but also in great diseases?
Matthias Lambert: I think I’m very, so I think there is two sides. I’m very excited by the gene therapy, uh, area because I think CRISPR, it’s an amazing tool to basically change the mutation, correct the mutation, the mutation you want, you can correct it. And we know how to do it in a dish. But right now it’s very difficult to get this correction to the cell in the body to basically deliver this compound, this technology to the muscle.
And so this is one thing that is very difficult right now. And we still more, I would say more development, uh, for the, I would say for the skeletal muscle area, for the neuromuscular disease area. Um, so that’s one thing. And the other thing is about CRISPR is right now. When you correct one mutation, it’s like I would say, like, uh, a personalized treatment because for a same gene you can have different patients with different mutations.
So basically you will need different design in your CRISPR to, to, to make it work. Um, so that’s, that’s one thing. So the second side I would say about drug, uh, so I’m talking about small molecule, it’s you can maybe find a small molecule like a common pathway across different patients. So it will be less personalized treatment, but like I would say a more common treatment across a population of patients.
And I think I’m very excited by combining both. So, having, uh, small molecules that could help the, for example, the delivery of the CRISPR in the muscle, that could be one thing. Or, decrease the toxicity, also, of CRISPR, that could be also another thing. So, I think The next step for me, as I see, is to combine a small molecule with a gene therapy.
There will be, you know, when you think about, for example, HIV, you have, it’s usually a tree therapy. You have three compounds that do different things. And so gene therapy is going to be the same, you’re going to have a cocktail of different drugs, different technology that will help each other to reach the same goal, which is to correct the mutation and to, to, to restore the pathology.
Naji Gehchan: So as you think about this, what are for you the biggest challenges you’re facing for you to be able to get there?
Matthias Lambert: Uh, money, funding, first, uh, people, second, uh, for, for example, for me, I would say on this disease, there is maybe five or six lives in the world working on my, on my gene for this disease. So there are only a few people working on it.
So the development is very, is, uh, slow, very slow. Uh, and also on a patient perspective. It’s even more slower, I would say, because you also, you have two different timeframe, you know, like one year for a patient is very long, you know, when in one year you can have your, like the series, you know, you can have, uh, the, your data that, that can, you know, be worse, you know, after one year, but for a scientist, one year, it’s nothing, you know, because one year you can get funding and you can get some preliminary data.
So it’s, It’s also a different thing. So first, yeah, coming back to, to your question. Uh, yeah, the, the, the, the people, the funding. So, I mean, both are, you know, together, you know, uh, if you don’t have money, if you don’t have money, you cannot, cannot hire people working on this. So yeah, that’s, that’s the main issue right now.
Naji Gehchan: And then, um, in money, I imagine you’re talking about funding, like having the funds for you to be able to do the research, build, build the company, have the people who can help you out with this. And I, uh, I really loved your framing between time perspective. So I want to talk more about this because as you said, for science, probably a year is nothing, but from a patient’s perspective, a year is a lot and a lot can happen this year.
So as you’re both, On this, uh, on this, uh, specific disease, I’d love to hear how you balance this and how you would push us actually as healthcare leaders to think about rare diseases, because it’s certainly one of those aspects that is hard to crack. Uh, and I would love to get your thoughts, what we should do.
Matthias Lambert: I think. Like, patients should be involved in the research, uh, that would be one thing, you know, like, uh, can be, you know, sometimes I go to conferences where, and you have both patients and scientists together, you know, and I think it’s a great thing to, to hear from the patient, you know, what, what do you need, what is the most, Like what do you need right now, you know, and sometimes you can be surprised, you know what they say, you know, sometimes for a patient just for him to just to eat, to eat alone, you know, on his own, uh, before being able to work, you know, uh, in my disease, for example, you know, uh, I can work, but the, the main issue is the, the breathing, you know, my diaphragm is very, very, very weak.
And during the night, you know, I have a, I’m, um, uh, sleeping with a by uh, a bipep. And so it’s a it’s a life threatening threatening disease, you know? And so I would like to have a for example, the technology uh, therapy that will target the diaphragm, you know, let’s say. So that’s one thing, you know? So when you can refocus your science to a particular goal, you know, that could, that can also meet the goal of a patient, you know, that’s very important, I would say.
And then you have to work with Industry, uh, and of course, like agencies like the FDA to, to accelerate the path, uh, to have, you know, right now we’re talking about end of one treatments, uh, things like, like that. But again, NF1 treatment will treat one patient. And so, you also have to have this balance also in what you want to do, you know.
You have to think about, you know, a path that can, that can work for every patient. And this is, I think, very difficult right now.
Naji Gehchan: Well, thanks for sharing this, Matthias. As you think through the next steps, with, so now you know which gene, you have some ideas about targets, what you want to do, how are you thinking about clinical research and drug development in this space, and the next steps after this huge discovery that you’ve, you’ve done in the
Matthias Lambert: So, so after I, um, I knew, I knew the gene, so I went to Boston working on condition with sclerodystrophy, and at the same time, uh, I talked to my boss and said, okay, I would like also to work on my gene and, you know, on my disease.
And at that time, there were no, no model, uh, no animal model, no cell, uh, Cell models about, about this disease. So what I did is to make a mouse model. And the cool thing about it is this model basically recapitulates, uh, the, the symptoms and the phenotype that we see in patients. So that’s, that’s one thing.
Um, and so with this model, so you can do one thing is to better understand the disease, because right now, you know, as I say, it’s a very rare disease. So we don’t have a lot of. patients in the world, which means we don’t have a lot of samples to study. So it’s very difficult to study right now this disease.
And so when you have a model, you can spend more time to study the disease. You have more samples, you have more materials, you know, to work on it. That’s one thing. And then the second thing is to treat. Uh, so you, my idea is to, and this is what I’m doing right now, is to develop different strategies to, to, to rescue the phenotype in this model.
And once I will get, I would say, a solid, uh, data and good preliminary data, that’s my goal will be to, to meet with industry and say, can we do something, you know, can we develop something that can go to the patient?
Naji Gehchan: Uh, yeah. Great. Um, it’s really massive work and great job that you are doing. I’m glad you’re advancing the science.
And again, as Uh, you’re passionate about it and you’re doing moves and it’s important to follow the steps. And I know, uh, the timelines are longer than you would ever hope and we all would ever hope. But, um, I’m really glad to see, uh, where you’re going with it and wish you all the best for it. Uh, I would, I’m gonna pivot now, even though hard to pivot.
Uh, but I would love to give you one word and get your reaction to it. The first word is leadership.
Matthias Lambert: Uh, leadership, I would say maybe leadership in science. Um, leadership in, um, I would say something pretty new or so, like, uh, inclusion in science, I would say. Talking about inclusion and again, we are talking about the patients being included in the research, but also being having like people with disability, you know, included in science.
And I think it’s very important to have right now this People, you know, working in, in this field because for the past 10 years, this is, so it’s, um, there is, um, a paper from, uh, that that’s been published and seeing that basically scientists with a disability are the only minority that has decreased.
over time in science, and you have a very few, just very few, uh, scientists with disability, uh, funded by NIH in the U. S., and I think, again, it’s very important because, you know, you need to have a leadership from institutions, from agencies, uh, in this because when you have, uh, the patients. I went to science.
This patient had to face so many barriers, so many challenges. And so, I like to say that patients, it’s a very good, it’s a very good problem solving. Uh, because we have to solve so many problems. Problems in our life because, uh, because of our health condition, this is, I mean, just for me, you know, when I go somewhere with a wheelchair, you know, sometimes I have to take a different path because you can have a step.
And so, you have to solve a problem, you know, and the, you know, you have to solve, like I was saying, life, you know, like, uh, um, in, in, in the moment. And so I think you need, we need to have more people like that in science and we need a leadership. We need people from the top that say, okay, let’s do this. Uh, we need to create a path, we need to include more, you know, we need a task force about this.
Uh, I think it’s very, very important. Uh,
Naji Gehchan: that’s such a strong reminder, uh, Matthias, for all of us. The second one is innovation.
Matthias Lambert: Uh, innovation, uh, I would say now innovation is going pretty fast. I mean, every year you hear about a new technology, you know, a new, a new innovation. Uh,
I would say that in the field right now, the innovation, to be honest, like the last 10 years has been CRISPR. Again, that has been the big innovation that I would say can, at some point, cure, I mean, that’s a big word, but cure any, any disease. Um, but what we are missing right now in term of innovation is how to deliver this in the right tissue.
And I think tomorrow, uh, if you have a company that fine, you know, like the right, uh, the, the right animal, molecule technology to deliver this, that’s gonna be a game changer. That’s gonna be a game changer because right now we know for any mutation, we know how to correct a mutation in the dish. Uh, we know how to correct.
the mutation in the mouse because the mouse is pretty small. Um, you have also less, uh, uh, I mean, response in the mouse, but when you go to the patient, to the human, it’s totally different. And, uh, there were a lot of cases right now, like in the past five years using, you know, genetherapy and the CRISPR that has, you know, adverse events.
And death, uh, in patients. And I think right now innovation tomorrow is definitely the delivery. If you have this technology, the game, the game is done. Well, there is
Naji Gehchan: a lot of work ongoing. The third one is rare diseases.
Matthias Lambert: Uh, I would say what, what is a rare disease? You know, that’s a big, you know, big question because I am in the field, but every day I learn something new, but rare disease, um, and depending on the, on the country, you don’t have the same definition of a rare disease, depending on how many patients you have, you will say, Oh, if you, you have this threshold and the threshold of number of patients is different in the U S compared to Europe, for example.
And so now we’re also talking about ultra rare diseases. Like mine, you know, when you have a few patients, and when I say a few patients in the world, it’s maybe 100, maybe maximum a thousand. And so, when you talk about rare disease to a company, and you say, oh, there is 500 patients like me. In the world, you know, they’re going to look at you and say, okay, but I’m going to get my money back, you know, uh, which is, which is true.
Uh, but so we need to have an ecosystem for rare disease that right now doesn’t exist. Uh, a path that can work for both, you know, we need to unite, you know, academia and industry on this question and, you know, involve, you know, investors. Uh, the FDA, of course. But right now, that’s, I would say one thing that is missing for rare disease is the ecosystem.
Uh, how to, how to make a, a, a compound technology treatment that can be, that a family can afford. Because when you think about some of the gene therapy, it’s like millions of dollars. And so, uh, it’s, uh, It’s a lot of money, of course, but also in the other, on the other side, you know, you need for the, for the, for the company to invest the money, you know, they’re going to invest the money and they need at some point the money back, you know, to find a path for this.
So we need a new, we need to think out of the box for the rare disease. And again, I think having patients. in the, in the discussion is very important.
Naji Gehchan: The final one is spread love and organizations.
Matthias Lambert: I would say, um, that’s a difficult one, you know, uh, I would say, you know, like Humidity is one thing, uh, because again, I’m having the view of a patient, you know, every day you, you, you know where, why you are here, you know why you are in the lab. And so you ever saw this? empathy. Uh, and sometimes you have, you have too many empathy, you know, when you have a rare disease, you know, uh, that can, you know, destroy you.
Uh, and so, but I think empathy, it’s very good to, to spread a good vibe and love in an institution. Um, and I was Thinking, yeah, um, again, empathy is, you know, every time, you know, I see, you know, when I have a difficulty, you know, in institution, you know, especially talking about my, my disability, you know, disability, I say, you know, you should maybe for 30 minutes, you know, take my wheelchair and you’re going to see what I see.
Um, and then maybe it will open, you know, your eyes. On the world that you don’t know, and it’s okay to, to, you know, you don’t know about the world of disability, you know, but it also opened my eyes in the world that, that I don’t know. And so it can be in terms of culture, it can be in terms of, you know, uh, belief.
Um, it’s basically how I accept. different, you know, views, but trying to learn about those views will help you. And so, you know, again, talking about inclusion, you know, it’s good to have, you know, when you talk about disability, it’s not, it’s good to talk not only to people with a disability, but also to other people that don’t, don’t have a disability, you know, trying to open this world.
So, yeah. Open the word. I will say it’s, uh, and I think open your, your world to others. It’s a good way to, for them to understand you and to spread, uh, love. Yeah.
Naji Gehchan: Well, mats, open up your word. That’s such a beautiful charge. And ask, uh, for, for us, uh, any final word of wisdom. for healthcare leaders around the world.
Matthias Lambert: Um, I would say listen, listen to the patients. Um, definitely include patients because, as I say, we are good problem solvers. We know where to go because we don’t have time to make a detour. Because when you have a rare disease, usually a rare disease is no joke, it’s life threatening, and you, you have to go to the point, directly.
And so, sometimes, I mean for me, it worked, you know. That’s a quick example, uh, for 25 years, you know, my physicians, My medical team in France didn’t know about the gene. It took me a few months to read some papers and figure out, you know, the gene that caused my disease, you know, and that’s one example, you know, I believe, you know, that, you know, when you listen to the patient, when you include patients, when you include, include patient scientists, you know, you know, our metrics Or not, you know, publishing in nature, uh, or metrics, or, um.
to save lives. And so that’s totally different, you know, uh, our metrics also to, um, I don’t know if I’m going to be able to make it today, you know, because I’m going to be too tired to go to the lab. Or, you know, uh, you know, our programs are different when our viewer is, is, I mean, our view is different.
And so again, if you include this view, um, and it’s on, you know, how to make, you know, the right decision for this, you know, Type, you know, this question, you should, yeah, it’s, um, usually the patient know more about their own disease than any physician in the world. So that’s, that’s one thing, especially when you have a rare disease.
So, yeah, again, I’m repeating myself, but listen, listen, listen to the patients.
Naji Gehchan: Oh, my chest, uh, can’t thank you enough for this inspiring and incredible chat. Uh, our metric is to save lives. This is how you framed it, and this is the main focus and, uh, KPI we should look at. Uh, thank you again for all you’re doing.
Um, it’s, you’re advancing certainly science and you’re improving, uh, lives, if it’s not immediate, in the near future, I hope, for several people around the world. So thank you so much again for joining me today and being with me on this show.
Matthias Lambert: And thank you so much for, for this opportunity. And I hope that, you know, if there are, you know, any, any patients, you know, listening to this, um, don’t, don’t be afraid, you know, if you want to, if you have an idea, go for it, go for it.
Naji Gehchan: You’re such an inspiration and a ray of hope for so many. So thanks again for joining me.
Matthias Lambert: Thank you.
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