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This podcast series features Mass General Brigham researchers whose work is redefining what's possible and how we care for patients. Our goal is to spotlight transformative discoveries, the people leading these transformations, and how they can improve patient outcomes, highlighting how today's research is shaping the future of medicine, including training the next generation of clinicians and scientists.
This podcast series is not accredited for CME/CE at this time.
SEASON 1: Crossing Medical Frontiers: Research Innovations Transforming Care hosted by Dr. John Co
SEASON 2: Learn, Discern & Return: An MGB Physician's Journey hosted by Dr. Erik Alexander
Welcome to Crossing Medical Frontiers, Research Innovations Transforming Care. My name is Dr. John Co, Vice President for Education at Mass General Brigham. This series explores the groundbreaking research being done here at Mass General Brigham, the visionaries that are doing that research, and the ways that that research can transform care. Today, I have the pleasure of being joined by Dr. Roger Hajjar.
Dr. John Co:He is the founder of the Gene and Cell Therapy Institute here at Mass General Brigham and a leader both here and internationally in this area of work. So Dr. Hajjar, thank you for joining us today. Really appreciate it.
Dr. Roger Hajjar:It's a pleasure to be here.
Dr. John Co:Yeah. You know, I always like to start with our audience getting to know you a little bit. And so could you say more about what led you to, you know, the career in medicine, first of all? And then to the research that you're doing now. Like, how did you get interested in it, and what led you to devote your career to this work?
Dr. Roger Hajjar:I started out as a biomedical engineer and I was very focused on the function of muscle movements. And that was really a fascinating work that led me towards thinking about medical school, especially vis a vis the heart and how the heart muscle functions. So I was very much focused on cardiac work and cardiac research as I embarked on my first research, component at Johns Hopkins. And then when I came to Boston, Harvard, MIT, delving into the molecular aspects of how the muscle fails. Specifically, I took over first, eight to ten years of my development and that led me to identifying multiple targets within the heart muscle that were deficient in the setting of cardiomyopathies, heart failure.
Dr. Roger Hajjar:And then the next step was how do we target them since we've identified deficiencies. And that's where gene therapy came in. We were lucky to utilize gene therapy not only as a proof of concept but as a therapeutic, very early on. And that has given us the opportunity to develop multiple techniques for delivery of these vectors, developing novel vectors also, and then finally addressing unmet needs within the field of cardiomyopathy and heart failure using these techniques and the know how that we basically gained over a few decades.
Dr. John Co:I'm curious with all the work you've done, you obviously started in research pretty early in your career. Did you continue that during even your clinical training? I know you've done a fair amount of clinical training in cardiology and subspecialty cardiology, but I ask because there are a lot of trainees that may be listening wondering, can I get involved in this kind of research even early in my career?
Dr. Roger Hajjar:I mean, I was fortunate to be involved in research very early on as an undergraduate and continued that line of work very focused, for many years, including the time I was in doing clinical work and I was, training. And I feel like the training, especially as I got into my cardiology fellowship and heart failure training, allowed me to to view how important the research we were doing in a clinically relevant patient population. That is really important to have that sort of parallel pathways where you are seeing patients clinically and you understand the unmet need. And then on the other hand, you may be doing very basic research in terms of understanding some of the disease pathologies, but also you may be developing novel therapies based on what you see clinically. The MGB system is an ecosystem that really gives you that opportunity, and anyone who is interested should really look into it because there are multiple opportunities within our ecosystem.
Dr. John Co:Yeah. So you're highlighting the importance of if you're doing research, particularly health related research, to be doing it in a place where you can really be with people that know how to translate it to the bedside and know the important questions to ask. When I think of gene and cell therapy, I think of something that's, you know, almost like futuristic, actually. And I'm curious, like, tell me, when would you say you started doing your work in gene and cell therapy, and how did it, when did it become more of a, like, a a reality? Was there an inflection point in the research in this area?
Dr. John Co:And, so when was that?
Dr. Roger Hajjar:I was not born as a gene therapist. Okay. There there are some people who start out their careers as a gene therapist, but I was a cardiologist really focusing on heart failure and why the heart fails. And as I mentioned, we found a number of targets that we wanted to go after. Initially, we did that pharmacologically and it failed.
Dr. Roger Hajjar:But we had done proof of concept using gene addition or gene deletion and we said, well, why don't we do the same thing but from a therapeutic perspective? And that's where we brought in the gene therapy component in cardiovascular disease where, you know, this was twenty years ago, when no one was thinking gene therapy for the heart and this was at that time, it felt futuristic. Now I feel like it's much more commonplace. So that's really how for me as a clinician scientist, I started using gene therapy because it was a means to an end. Gene therapy allowed me to deliver specific genetic material that augmented pathways that were deficient in heart failure, and that's how we we got into gene therapy space.
Dr. John Co:You're actively doing research now, obviously. Right? So what are some of the questions that your research, your team is trying to address and answer? And if you're successful, how will answering those questions transform care, in cardiology or or other areas.
Dr. Roger Hajjar:Maybe I'll take a maybe step back and and discuss the Gene and Cell Therapy Institute at Mass General Brigham. This institute was founded about two and a half years ago, based on the fact that we have about 500 investigators in the gene and cell therapy space within MGB. Gene and cell therapy is really a transformative medical treatment that's coming being available now, and we have over 30 approved gene cell therapy products across multiple disease states. So it's a real a reality that's evolving, and we wanna make sure that our investigators within MGB have all the tools to take the next step and realize that they can utilize different modalities to treat patients, including gene cell therapy. So our institute is made up of a research team, multiple cores, a regulatory team, and a manufacturing team because these are the barriers to transforming work in the lab to first in human trials in patients.
Dr. Roger Hajjar:So we work with our investigators to make sure that they have a regulatory path with the FDA to get to that first in human trial. We make sure that they have the manufacturing needs. As you can imagine, it's not just one modality. There are multiple different, modalities in gene cell therapy across MGB, different vectors, different cells. So we have to make sure that we, help our investigators get the right manufacturing.
Dr. Roger Hajjar:Clinical trial design is extremely important in gene cell therapy, so we help our investigators with that too. And finally, there are funding mechanisms within the institute to kick start some of the work towards, INDs. Our goal within the institute is really to help our investigators get to that first in human trial in patients with very big unmet needs.
Dr. John Co:Well, Dr. Hajjar, thanks for providing that context for the overall work of the institute because I think what you're raising is that your work is just sort of one area. Can you tell me more about -- I'd love to hear more about if your lab were to answer the questions it's seeking to answer, what do you think are the possibilities for how it would transform care?
Dr. Roger Hajjar:Because gene and cell therapies are more or less, one or one treatment or two treatments, it will really transform the way we sort of view treatments and chronic illness. Because the gene and cell therapy work is, first was focused on genetic type of diseases, monogenic diseases and now, we're into the chronic diseases where we're targeting pathways as opposed to just one gene at a time. So it does have the potential to really transform the way we view chronic diseases by being able to treat one time and have the patient reverse many of the pathologies that they've had, either from chronic condition or from genetic mutation. So from that point of view, we've seen with the early genetic therapies that we have that transformation occurring. So clearly a transformative type of treatment that will really change the way we treat patients and we follow them long term.
Dr. John Co:Well, so for patients with some of these chronic conditions that you're talking about, would this mean that they would otherwise be cured where there actually is no sort of cure now? And or is it also that they would no longer have to take medications? I'm just curious how you see that for some of these conditions.
Dr. Roger Hajjar:So for genetic diseases, that would be absolutely right. You would could basically correct the mutation or augment the deficient gene that would basically not require any medical treatment. In chronic diseases, as we know, there may be multiple etiologies that are occurring. You may be able to reverse the condition with genetic materials for a specific organ, but other organs may still be affected and require medication. So from that perspective, yes, there is the possibility and in fact we do cure diseases based on genetic mutations.
Dr. Roger Hajjar:In chronic diseases, it's a little bit more complex and may require an interplay between gene therapies and other types of treatment modalities, whether it's pharmacological or device therapies as used a lot in cardiology.
Dr. John Co:You did mention, though, Gene and Cell Therapy Institute with how many investigators did you say?
Dr. Roger Hajjar:We cater for over 500 investigators across Mass General Brigham.
Dr. John Co:I mean, there's so many people doing work. Are there specific investigators, specific lines of research that you would like our listeners to hear about? Like, of the more exciting things, things that you you think they may find surprising that we're working on.
Dr. Roger Hajjar:Sure. I mean, I'd love to highlight a few of our investigators. That's really the the beauty of working in a place like MGB where you have key opinion leaders in many of these diseases here. So in terms of, some of the neurological diseases where we see quite a bit of gene therapy work in, first, like to point out there, pediatric, neurovascular diseases whereby, these patients develop very or subacute forms of, strokes at a very young age based on a mutation in ACTA2. And doctor Patty Musolino, who works at MGH Pediatric Neurology, is focusing on editing the gene to correct it in kids in vivo with a really nice setup where the gene editors are also prepared or developed within MGB by Ben Klankster. And, that team is really advancing very rapidly towards clinical trials.
Dr. Roger Hajjar:The other program is in gene therapy for pain. Chronic pain or different types of pain are being addressed by delivering specific channels. That work is being headed by Brian Wainger, also at an MGH, and focus very much on how to treat pain with a one time delivery. Within our institute, we have specific cores. And one of these cores, the RNA therapeutics core, delivers these very specialized circular RNA that can be made very quickly and reliably but deliver any type of cargo to any organ with a very robust expression pattern, very much a follow on in what we saw with the modified RNA in the vaccine.
Dr. Roger Hajjar:And that modality is now being used in over a 100 investigators with an NGBA from zero to over a hundred or two years. So this is the kind of, work that the institute is doing to really provide the framework for our investigators to quickly be able to go from identifying targets to developing treatments, for these targets.
Dr. John Co:Wow. Well, that's just, I mean, and that's just a small sample of what's going on with incredible, breadth and depth that you've described. Is there anything else you'd like our listeners to know about where this field is headed and what you're hoping to see in gene cell therapy in the next five to ten years?
Dr. Roger Hajjar:One of the areas in gene therapy and cell therapy is really the in vivo gene editing is very promising. And by that, I mean delivering vectors that can and editors that can basically correct the mutation within the body. This there was a beautiful example of that a couple of months ago at CHOP and UPenn where the young infant at six or seven months old, had a urea cycle abnormality and that mutation was corrected with an in vivo gene editing and basically allowed the child to have normal urea levels and basically correct the application. And this is really an exciting part of gene therapy work because we're gonna see more and more of these in vivo gene editing come into play in patients, including very rare diseases where the identification of the mutation to actually delivering that therapy is not going to be in decades' time, but really it's going to be in weeks to months. And to me, that's very exciting, but it's a big challenge.
Dr. Roger Hajjar:So we have to be able to identify the genetic mutations very quickly to come up with a treatment strategy, then deliver it in a very short time or develop the vectors and the genetic material in a very short time. But that's really new shot type of approach in the near future, and that's what's very exciting that's coming up in the gene cell therapy space.
Dr. John Co:Well, I'm a pediatrician, I have to say, I'm so excited that several of the projects you mentioned or the areas of work and inquiry are in pediatric patients. Children with rare disease are often a population where there really isn't enough work going on, and I think gene into cell therapy, particularly for metabolic diseases, as you mentioned, it's a perfect sort of fit for that type of work to make a huge impact. Well, I wanna thank you, Dr. Hajjar, for coming today. Really appreciate you sharing all your thoughts and, you know, your knowledge and the work that you're doing, with our audience.
Dr. John Co:And hopefully, we can have you back. Thank you so much.
Dr. Roger Hajjar:Thank you. It's a pleasure.