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Crossing Medical Frontiers: Research Innovations Transforming Care
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.
Hey, everybody. Welcome back to Crossing Medical Frontiers. I'm doctor John Co, Vice President for Education at Mass General Brigham. In this series, we uncover the groundbreaking research that's reshaping medicine and meet the visionary minds behind these advancements.
Dr. John Co:Today, I'm joined by Dr. Patty Musolino, a critical care and vascular neurologist at Mass General Brigham. Her expertise is in applying human genetics to treat cerebrovascular and neuroinflammatory disorders. Doctor Musolino, it's great to have you here. Thank you for coming on the podcast. Appreciate it.
Dr. Patty Musolino:Thank you so much, doctor Co, and the team for having the opportunity to speak and converse with you guys.
Dr. John Co:Well, doctor Musolino, you know, I'd love our listeners to learn a little bit more about you. You know, what motivated you to go into medicine? How did you get interested in the things that you're doing work on now? And maybe you could talk a little bit about your training too. Like, I know you trained here at Mass General Brigham and wonder how that influenced what you're doing.
Dr. Patty Musolino:It's a journey that is is very daring to me. Like, I was in Argentina, Buenos Aires when I had to decide what to study first, and I had a passion for teaching. I was seriously considering becoming a a teacher, a rural teacher. And at the same time, I had this incredible ease for the academics in general, but also a passion for biology. And there was a spike about the brain and how do we get to cognize the world around us?
Dr. Patty Musolino:What does it mean to be conscious? What does it mean to emote? How do we move our hand? I have all these questions. I was working in high school with an incredible biology teacher on the genetics of Drosophila melanogaster.
Dr. Patty Musolino:It's a -- this is the fruit fly.
Dr. John Co:Yeah. I know Drosophila. Yeah. I learned that for sure.
Dr. Patty Musolino:And we were getting the flies from the the physics main institute research institute in the country, and they had genetic variations that make them have different colors of eyes and different shapes of their wings. And we work with these flies and kept them and crossed them and deducted their genes from their appearance, so phenotype to genotype. Yeah. And back and forth for almost a year and a half, and that was very early. So it was that kind of fusion of: I love working with people. I'm fascinated by the brain development, seeing a baby, a child take the world and develop from scratch some of the skills, the very basic skills we were given, that we have.
Dr. Patty Musolino:And then I started medicine. We have a seven year direct out of high school career in training and where the first four years are very equivalent to an undergrad with very heavy focus on premed. And that was in my native Buenos Aires. The bug of research was there very early on, even from high school, as I mentioned. And so I started teaching anatomy and then internal medicine, and then my mentors offered me a PhD, so to really dive into research.
Dr. Patty Musolino:And this was in collaboration with the Karolinska Institute in Sweden. And in combination and co mentoring between the university in Buenos Aires and the Karolinska Institute, I finished a PhD in neuroscience, and it was almost like a natural progression to seek training in the United States and come to the best places I could, get trained on for my clinical training. And and that's how I apply, and I interview for child neurology, which starts with pediatrics. Yeah. Then continues with a year of adult neurology, and that's where the passion for vascular and critical care came from. And I continue with child neurology and remain a hybrid, and I see patients in any stage of their lifespan.
Dr. Patty Musolino:So prenatal, from being an infant, a child, a teenager, a young adult, or senior, and if they are affected by severe illnesses primarily that compromise the vasculature in the brain. Those are my patients, and that's a little bit of how I got here. Training in MGB has been incredible. Like, to me, the the wealth of people, and I wanna highlight this. I'm not talking in chess about doctors.
Dr. Patty Musolino:I'm talking about everybody taking care of the patient, the nurses, the assistants, the volunteers. I remember vividly walking into the hospital and meeting the front desk and this person really trying to help me get to where I needed to go. And I interview in many places, and it didn't feel the same passion and dedication for doing your job to the fullest, to the best, taking the person that you had in front of you as someone that you can help. And and that was very marked. And then walking on the hallways where some of the origins of medicine happen.
Dr. Patty Musolino:For someone that comes from abroad, might not be as familiar with the classic academic old institutions, this to me was a place where you could learn the the unteachable. It's in the walls. It's a romanticized way of saying the legacy is here. The legacy of how these first thoughts were made into reality were made in these walls. I do think the the people, the passion for teaching, the passion for the patients themselves, and and for making the everyday unique, exceptional, even during the most difficult times that one can have in your own life or in life of patients or or the health care system.
Dr. Patty Musolino:The challenges can come from any place, but you could see how we come together and I got to experience this during training. We have situations like the Boston Marathon bombing, and I was a neuro ICU fellow at the Brigham and receiving the patients in emergency room and just seeing how a hospital can flip on a dime and put every single resource to make everybody so alive. Yeah. Every patient that got to the hospital with all the tragedies that happened were able to be taken care of. And this was across town, not just Brigham or Mass General, and I can I could see the the the real transformative quality of the people and the place that we're in situations like that,
Dr. Patty Musolino:And I see it every day when my patient walks into the room and and they are happy to see me again after I haven't seen them for a few months.
Dr. John Co:Well, that's wonderful. It's incredible how it sounds how very early, you know, in your life, you, you know, gravitated towards medicine and actually even research. Pretty pretty specifically too. Can you say more about the research you're doing
Dr. John Co:now? And, like, what are the key questions you're trying to answer with your research? And if you're successful, how is it gonna impact care in patients here and and beyond?
Dr. Patty Musolino:So we are researching and studying, investigating how the most severe forms of vascular disease, the disease that affects the vessels in the body and the brain, affect the brain and cause disability. Vascular disease is the number one cause of death and disability still in the world these days with every single therapy and medical optimized care that we can provide. And that tells us that there is a lot of unmet need, and there is a lot of questions and basics mechanisms and things that we could do now that we have incredible tools at the molecular biology level to, for example, individualize the treatments, doing it based on your own genetics, your own genes, your own features, and changing DNA in your own body. That's now happening. It's no longer something we could do in the future.
Dr. Patty Musolino:It's something that we have the tools right now. And that unmet need that we still see these patients suffering vascular disease everywhere in the body and in the brain. And recognizing that some of these diseases are happening in a very, very young age. Some of the research that we work on is understanding the disease. That's by seeing patients, by working with them and their families to really go through the journey of what's having the disease and taking care of them in a multidisciplinary way to understand what is the disease doing to that specific child or to that specific teenager or young adult. And the most severe forms of disease are sometimes caused by a single gene, a single letter sometimes in the DNA, very commonly, that is altered, that changes the function of that gene protein.
Dr. Patty Musolino:And the research that we do is in doing changes in those DNA letters to put them back to work how they should. And the whole aim here is to prevent disability, to prevent injury, to allow people to live to the fullest, to allow these children to develop without brain injury. And at the same time, we take care of them as we try to develop these therapies that could change their lives. And in taking care of them, we are able to also change the trajectory of the disease. We are able to understand how to prevent some of these, for example, strokes that are happening in infants.
Dr. Patty Musolino:We're able to change management on the standard of care that we provide. We have the best interventional surgical imaging teams and resources to really get to questions of pathophysiology that we cannot do in other settings. It is our duty to unravel this and work with the families and the patients. What is meaningful to them that we should be doing now? And at the same time, how do we do therapies that could hopefully provide a cure, but if not a cure, could change the most relevant symptoms that they suffer from?
Dr. John Co:Wow.
Dr. Patty Musolino:And ameliorate them. So that's the focus of the research -- is translational molecular individualized long term therapies that can change DNA or RNA and and modify the disease trajectory.
Dr. John Co:So it's incredible. So these you just mentioned as to, like, what you're trying to to study and achieve. How close are we, or is it already happening, in terms of clinical care being impacted with what you're discovering here?
Dr. Patty Musolino:Absolutely happening. And I wanna say that so the we we have this aim of delivering these enzymes, some of them called CRISPR Cas, that can change the DNA in the cells where they need to be changed. And we are aiming to do this for the vascular system, which has never been done for genome editing in humans. And we are in in a trajectory right now interacting with the FDA in some of the most severe forms in less than two years from the first in human studies. And we will learn a lot and we hopefully unlock how to target these cells and how to get these enzymes.
Dr. Patty Musolino:We will learn safety, what is safe, how can we do it. And then that could potentially unlock how to manipulate the vascular system that has been pretty difficult to heal once it's diseased. And that's why it remains the number one cause of death and disability in the world. Every few seconds, there is someone having a heart attack, and every few minutes and hours someone having a stroke in the world. And in my case, these patients are very young because they're affected by these genetic conditions that make them more severe.
Dr. Patty Musolino:And on the day to day, when these patients, for example, come to MGB to participate in a natural history study, this is how we systematically look at how the disease affects them in their body, in their life, in the things that matter to them the most. We are also providing a standard of care, but with a multidisciplinary team that has now dedicated, some of them entire armies of investigators and scientists and clinicians and the teams in the clinical side. And you get these messages saying how meaningful it was to be, for the first time, not the ones explaining their disease in the room. For the first time, finding someone that offers to continue following them up, working with their local team wherever they are, to continue to understand and provide the care they need in their life now. And at the same time, they feel active.
Dr. Patty Musolino:Now, they are part of the solution. Now, they're no longer a passive recipient of care being sick. They're not patients anymore. Now, they're investigators. Yeah.
Dr. Patty Musolino:They become part of the journey of trying to solve the puzzle. And and there is something about a little bit of the paying it forward. They -- many of these patients know that they may not be the recipients of these therapies. Many of the patients know it might take us longer than what they need right now. And that still doesn't take the meaning that this has for them because they want to do something so others don't have to go through their journey.
Dr. John Co:Are there ... you know, obviously, you're doing your research, but there's other people that you do your research with and other people that do research related to yours in our system. Like, do you have other other research studies or investigators you would like our listeners to know about?
Dr. Patty Musolino:Yes. You give me the time? Yes. The the work that we do and because it's vascular, if you think about vascular system, it's everywhere in your body. And is this continuum. Like, these vessels that come out of the heart, they go and branch and branch and branch and go into every single organ and come back to the heart. We are doing this only because we have the experts in the biology and the diseases everywhere the vascular system is affecting these patients. Doctor Mark Lindsay, he's a pediatric cardiologist. He's the director of cardiovascular genetics at MGB, and he is the expert in the monogenic forms of these diseases and the cells and the biology at the vessel cells, smooth muscle, and the endothelial cells.
Dr. Patty Musolino:And we work with him on the aortopathies, and he has been one of the most fruitful collaborations we have had. And then he also has brought into the work the adult side of the cardiovascular research center, and doctor Rashma Holtrar has taken on PE being a critical care cardiovascular cardiologist that sees adult patients when they're very sick and is an expert in atherosclerosis and calcific disease. He's taking on developing gene therapy for babies with calcific atherosclerotic disease because it's the best way that we're gonna understand what we can do or not and that we can then unlock and translate to larger patient populations. Yeah. Teenagers and adults and patients with kidney failure require this.
Dr. Patty Musolino:And and then we I have my colleagues in the neurocritical care unit, Dr, David Chang, who has taken on the most sophisticated neuroimaging on this modeling on the animals. We work with the neurosurgeons here at the Brigham, John Ralston, Mark Richardson at MGH, Kris Kahle, Bill Butler, in developing the therapeutics that the patients need. Many of these patients need surgery to take care of the vessels not working or vascular malformations. But at the same time, also in the research side, developing the ways to to get these delivery methods. Like, we said, vessels are difficult to heal because it's difficult to get to them.
Dr. Patty Musolino:And we're using something that is unique to a place like MGB, a research hospital, which is tissues coming from the OR, from biopsies, autopsies, and testing things in human tissue makes that transition from the mouse or whatever model you're using, a cell model, to the human derisk. If we can understand if what we're trying to deliver really gets through the wall of a vessel in a human artery, in a human vein, in a human brain, we're able now to be much more certain that the translation will occur, that these studies, first in human, are more likely to be successful. And in delivering, we need the scientists, the engineers that can do these technologies, and that's not our hats. This is doctor Klansteiber. He's the engineer that develops the enzymes that can change the DNA.
Dr. Patty Musolino:You ask, is this happening? What is happening to patients right now? Doctor Klansteiber is the person that designed the enzymes that were used in this baby that recently received genome editing in less than seven months from diagnosis to treatment for a terrible metabolic disease. And he is in our team, and he not only in our team, he collaborates with many more people. And then on the delivery side, we have the former wire who has developed and is an expert on these little virals viruses, the adeno associated viruses, the AAVs, which is the most common delivery method in gene therapy currently.
Dr. Patty Musolino:There are more than six thousand patients treated with AAV gene therapy, including in our own groups, children, for example, with Canavan's disease. And people from Brigham, MIT, Doctor. Artzi, Natalie, taking us on a whole new field in her laboratory to develop nanoparticles that can get to the vessels because that will decrease the cost, make it more accessible, affordable, able to iterate as we find your variation in the DNA and we wanna change the next one and the next one. We have a nanoparticle, we can do it faster at lower cost, and and we are doing that as well.
Dr. John Co:Yeah. Well, it's incredible, the work that you're doing. And I think you've highlighted something very important, which is that there's the research you're doing, but you're doing it in an environment where you can collaborate to not only make your research better, but actually, all the investigators benefit from each other to sort of take what they're doing and and apply it to other areas. So some, you know, some may say, well, you're a neurologist. You're doing neurology research, and but you mentioned so many other specialties Yeah.
Dr. John Co:Where what you're doing actually intersects with other people's work, and actually that probably makes the work better and accelerates it for everybody and and really maximizes impact, which is fantastic. Thank you, doctor Musilino, for sharing your insights and your impactful research. It's just so inspiring to hear what you're doing. And to our audience, we appreciate your time joining us on Crossing Medical Frontiers. Don't forget to subscribe so you can stay tuned to more of our episodes down the line where we're gonna hear about even more discoveries that people are making here at Mass General Brigham.