Aaron Lazar on His ALS Journey and the Impossible Dream

Episode Transcript

Dr. Correa:
From the American Academy of Neurology, I'm Dr. Daniel Correa.

Dr. Peters:
And I am Dr. Katy Peters. And this is the Brain & Life Podcast.

MUSIC:
When you're down and they're counting.
When your secrets all found out.
When your troubles...

Dr. Correa:
Welcome back or welcome to the Brain & Life Podcast. And as you can guess by the different intro music this week, we are again featuring an artist and musician living with a neurologic condition. You just heard a segment of Let Your Soul Be Your Pilot from Aaron Lazar and Josh Groban from the newly released album Impossible Dream. Katy, did you ever make it to New York City for a Broadway show between the '80s and 2000s? I know I came up with my high school during that time, but what about you?

Dr. Peters:
I really wish. I wish. No, I did not make it. I was a little busy in high school, college, and then medical school, where the time goes? So no. But since that time, I have been able to go to Broadway and I will say that it is definitely a different experience than seeing it in my high school gym.

Dr. Correa:
I imagine so.

Dr. Peters:
But I did get to see Come from Away in '06 and it just is a great experience. I need to get out more. Yeah.

Dr. Correa:
Yeah. I mean, I did some musicals in high school and I can appreciate the level of work and talent that there is when I see a show on Broadway and just like okay, puts to shame any thought of singing that I did in the past. Today, our guest is Aaron Lazar that you heard singing on that piece and Aaron was in so many shows that you may have seen him on stage. If any of you who have been to New York, we get to hear his own story of his path to Broadway and even how he considered going to medical school. But more recently, he was diagnosed with ALS and has organized a group of Broadway stars to help him fundraise and raise awareness for ALS care and research.
Make sure you hear our discussion and stay tuned through the end with our medical expert where we welcome back Dr. Bedlack to talk about the unique phenomena of cases where ALS progression was stopped or even reversed, and how this might point to unique lessons to learn about ALS as research and the search for a cure continues. At the end of the episode, we will go out with the full song that Aaron shared with us from the album.
Welcome back to the Brain & Life Podcast. I'm really excited that this week, we have a guest again continuing our series of different musicians and artists. I'm in New York so you all know and have heard several times. I'm a big fan of the arts. Today, I'm joined by Aaron Lazar. He's an award-winning actor, singer and advocate, and in over two-decade career, you may have seen him in a countless list of episodes on many different TV shows including Filthy Rich or movies such as Everything Everywhere All at Once. But if you visited New York, it's possible you saw him in one of his many starring and support roles on stage in over 11 Broadway and National Tour credits, including the Phantom of the Opera Oklahoma, A Little Night Music, Dear Evan Hansen, Les MisÃ©rables, it's probably the list's way too long.
I'm more than happy that we have Aaron here today. He shared with the arts community that life and health for him had taken a new path and it was given a diagnosis of ALS. We've talked about that condition a few times, but we're going to get into more of that discussion with Aaron and with our medical expert in this episode as he's continuing to increase and advocate for more awareness about ALS. Thank you, Aaron, so much for joining us today.

Aaron Lazar:
Thanks, Daniel, so much for having me.

Dr. Correa:
So Aaron, I wanted to start to really getting to know a little bit more about who you are beyond the ways that we may have seen you on TV or on stage on different plays, really, who is Aaron Lazar?

Aaron Lazar:
Wow. Well, I'm a father to two incredible boys, 14 and 12. I'm a basketball dad, which there are plenty of hilarious Instagram videos about those tournaments and how they're all the time many hours away and sometimes you have a kid in one location and another kid in another location and you're all over the place. So we love basketball. I guess I would say I'm also a really loyal friend to a group of guys that I went to college with. There's more than... I think there's about a dozen of us that are just like brothers from another mother's and I'm super grateful for my friendships with these guys. What else can I tell you?

Dr. Correa:
Well, I'm wondering then let's go back to the acting, your work and storytelling and on the stage, what ended up drawing you to that line of work and engaging in the arts?

Aaron Lazar:
I look back at pictures when I was a kid and there's pictures of me performing at an age, like a young age, like 8, 9, 10. I don't consciously remember choosing performing at that age. It wasn't until high school that I started singing in the choir and then performing in the musicals and obviously then getting into it pretty seriously. When I decided to go to graduate school after Duke where I was pre-med, I sort of put all my eggs in the acting basket for a couple of years and then here we are. But I've been performing since I was a kid, I guess I loved it. I guess when I really think about it, my mom was putting us in some fashion modeling, runway shows and taking me to commercial auditions.
And she might've known well before I did that she had brought an actor into this world. I wish she would've told me a little sooner. I would've had a less agonizing decision-making year, junior year of college trying to figure out what I was going to do after go to medical school or go to grad school for theater. But that's where it all began. The first production I did was Snow White and the Seven Dwarfs at a community theater. My uncle was Prince Charming and they needed a seventh dwarf and I played Grumpy and got a lot of attention and met some cute girls, and here we are.

Dr. Correa:
Sometimes we follow where our friends are and just where we end up enjoying things. But you mentioned that that difficult decision time in college and deciding between being pre-med and maybe trying to go to medical school or going to graduate school for acting, what was it about acting that ended up helping you make that choice?

Aaron Lazar:
You got to listen to your soul. That's something I've really learned how to do much more clearly over the last couple of years. And I think my soul was really talking to me. I just had a feeling that this is what I want to do, this is what I'm supposed to do. But I had wanted to be a doctor, actually a surgeon for years at that point into high school. Back in high school, I was shadowing doctors and watching surgeries, and I was so focused on medical school that I actually specifically chose not to do theater in college because I wanted to focus on getting into a great medical school and didn't want any distractions. Of course, you can't really run from who you are. So a professor in the acting department, a guy named Jeff Storer, who's been a friend for 30 plus years now, he saw me in a voice recital.
Duke had given me a scholarship to major in music, help them establish an opera program, which I didn't even... I had never done opera, but I had a sort of big legit baritone voice. So when I got to Duke, I had my first real private voice teacher. I did all the pre-med stuff, but I was majoring in music to maintain the scholarship, not because I wanted to compose waltzes and mazurkas and be a music historian. And so I kept spending all this time in the arts buildings on campus, and Jeff cast me in a production of Carousel, a big production that Duke was doing, and Billy Bigelow was sort of just a dream role of mine, the movie musical with Gordon MacRae, the great Rodgers and Hammerstein Hollywood movie musical Carousel. That was just a role that I couldn't pass up. And so I thought, "Well, I've got to play this part."
And one thing led to another, and Jeff basically started to plant the seed that I should... He basically said, "You should do this for a living." And that's when we started to put the wheels in motion. But my parents, nobody in my family other than Prince Charming, my uncle who was not a professional actor, nobody in my family knew of the business. So my parents were obviously reticent, and I was like, "All right, look, I'll take the MCATs," which are good for three years, and then that gives me two years to go to graduate school if I can get into this full ride scholarship at Cincinnati College Conservatory of Music. And then I've got one year after that program to move to New York or Los Angeles to try and get a job. So I'll never forget, my parents were like, "Yeah, okay, you've got a backup plan. So that works with us."
And I was succeeding. I mean, I was standing out in whatever I was doing, and so it felt like this was what I'm meant to do. But there's that moment. I'll never forget the moment. I was in New York pounding the pavement, living in a roach motel of an apartment. I mean, the whole cliche. And I got my first Broadway national tour of a musical called The Scarlet Pimpernel, and it was the end of the tour. So six months later, I came back. So I'd been in New York now, went to grad school for two years, moved to New York for six months, hustled hard, got my first big job, came back, and it was like the day that I got back that those MCAT scores expired. And I knew right at that moment, I'm an actor, there's no turning back.

Dr. Correa:
Wow. The deadline of a great expiration being such a definitive moment for you. That's interesting.

Aaron Lazar:
Well, listen, you've taken that test, right? You know what that was like.

Dr. Correa:
Yeah, you don't want to take it again.

Aaron Lazar:
You don't want to take it again. That's right.

Dr. Correa:
In 2024, you came out publicly about this diagnosis of amyotrophic lateral sclerosis or ALS. Let's go back to when you first started noticing some of the symptoms that ended up leading to this diagnosis. What is it that you remember starting and feeling?

Aaron Lazar:
I had gone through a breakup, and to be completely candid about it, I had a sense that even though my life was a bit of a roller coaster, and it had been since a divorce a number of years prior, and I was always able to find my footing when I was playing a role. So when I landed a job, if that was Dear Evan Hansen or one of the stars of Fox's series, Filthy Rich, life made sense and I knew who I was. And if I had a significant other relationship in my life, I was grounded at in knowing who I was. And long story short, the pandemic hits. I go through a breakup and I have this very strange sensation that my life is stuck in a pattern and I don't know how to get out of it. And two weeks later, my muscles started twitching. I had full body muscle fasciculations for about six months with anxiety, insomnia, and depression.
And you're seeing neurologists, and they're telling me I have benign fasciculation cramp syndrome because ALS requires more than one symptom to diagnose. But I just had the twitches and my strength was really good. And then I go for a jog in Christmas of '21, and I start to notice that my left foot is hitting the pavement harder than my right and foot drops another symptom. And so the diagnosis came pretty quickly thereafter. But that entire summer of first symptoms and it getting worse and me confronting my own mortality and being deeply, deeply afraid of what was happening to me, I kept saying to doctors, "I think this is just a Spiritual Exercises. I think there's something going on here." And I've been a seeker for a long time since before my kids were born. So I think it's both. I think it was physical manifestation of dis-ease in the body, partly connected to something that my soul is here to learn from and grow from. And man, have I been learning a lot for these last couple of years.

Dr. Correa:
Yeah. And as you've been seeking on your own spiritual path and learning from that, how has it been separating that from some of the physical symptoms that have come out or developed from the condition?

Aaron Lazar:
I think I learned from having a body that I had sculpted and shaped since I was 14 years old, learning to love myself despite what's been happening to my body comes from a place of awareness that I am not my body. I'm something else. I'm the awareness that I'm not my body... I'm consciousness. And so I've basically spent the last two and a half years reading books on healing in the nervous system by doctors and yogis and spiritual teachers and renowned scientists, and learning as much as I can about how to heal myself as much as I can while medicine does everything it can to help people and help end this disease.
And a lot of what I've learned has to do with health being more than just physical, it's also mental, emotional and spiritual. And so I've spent as much time as has felt right and truthful to me healing myself mentally, emotionally, and spiritually. And whatever that means, it's different for everybody. But in doing that, it has given me a real set of tools and a number of gifts to help me through the physical challenges that this disease can bring with it.

Dr. Correa:
So it's not so much that somehow you've cured the depression, anxiety and the grief that comes with it, but now that you've armed yourself with tools to help take care of yourself.

Aaron Lazar:
Well, I think it's as important to be specific about, I do not have anxiety, insomnia, or depression anymore. A neurologist put me on Lexapro within a couple of months because it was so bad and I really was a person, and I say was because I'm no longer that guy, but I was a person who ran everything. I took everything very personally through my nervous system. So anxiety was physically shutting me down. But so getting on Lexapro was something that I... There were so many stigmas in my world of mental illness and don't want to take the drugs. And I speak very publicly that I could not self-regulate. I needed help. My brain chemistry was off, when you run your engine as hard as I was running mine, and you deplete your brain, whether that be of dopamine or melatonin or serotonin or whatever it is, it's a machine.
And the machine had broken. And that particular drug for me, it took me probably a month to get up to a dose and it was uncomfortable, but it worked. And then I stayed on it for six months, tried to stop taking it, weaned myself off. The anxiety was still there, so I stayed on it for another six months and got off it about, I don't know, two years ago. I don't even know at this point. But that drug was very important at that time in my life. And I'm thankful, and I believe it's important for people who cannot self-regulate, and I want to be an advocate for the meds that are there for the right meds, for the right reasons. Now, it's been like spiritual warrior ninja training for two and a half years to be able to handle life, the ups and downs of life.
Like I said, I really couldn't handle life before unless it was going the way I wanted it to go. And this disease has been an opportunity to live in the present moment because that's really all we've got anyway. And I had spent all my time catastrophizing the future or beating myself up about the past, and I was missing the billions of moments that are the present that make up most of our life. And in order to be in the present moment, you got to have a quiet mind. And ALS threatens to take that away from you all the time because with each step that you take, and thank God I'm still taking steps, you take those steps and you notice something isn't right. It's misery and my heart goes out to anyone dealing with it or family dealing with it. And so I don't want to spend whatever life I have left, not enjoying it or to put it positively, I want to enjoy every moment of my life, ALS or no ALS, how do I do that? I have to practice the art of enjoying my life all the time.

Dr. Correa:
Yeah, I'm glad that you both found the medications that you needed at the time that you did, and that since then you've built an armament of tools in coping to be able to practice that. That's great.

Aaron Lazar:
I mean, thank you. Look, the tools, I think it's important to say that the tools are readily available for anybody that's looking. On my website under the healing section, I've listed most of the books that I've read. Many of those books, although written by 50 different authors, all say the same thing. They're all teaching the same thing. There are tools, be it meditation, whatever it is, and ALS, it slows you down. So I wasn't able to live life at the pace that I used to. It takes away your physical distractions, if you will, your activities, the gym and tennis and hiking and all these things. And so you're sitting a lot more than you used to. And it's like, "Well, what am I going to do at this time? Well, I'm going to practice creating for myself health, mentally, emotionally, and spiritually, and then as within, so without," and it sounds easier than it is, but that's the work that helps me to enjoy my life, have an impact on other people, still be creative, still be present, and I'm grateful for that.

Dr. Correa:
We've ambiguously described a set of tools. You've mentioned meditation and just being able to sit with yourself and your expectations as one of those things. But is there a specific example of a practice that you work towards that has helped you with this?

Aaron Lazar:
Yeah, I mean, I think that's a great question because meditation is very vague and a lot of people still, even though it's certainly more popular than when I was growing up, I still think a lot of people don't really know what it is. To me, meditation is very, very specific. And I've really spent the last year becoming sort of an advanced practitioner of meditation because I used to use meditation as, well, I just need to quiet my mind and people say, this is good for me to do, so I'm going to sit in a chair and try and have no thoughts. And that would maybe work one out of every 50 times and I would have some quiet experience. And the rest of it was like, I'll either fall asleep or I'm frustrated because I don't know what I'm doing. So that's the beginner meditation experience.
But I'll tell you, when you're diagnosed with a disease like ALS and the whole world says to you, you're a dead person. This is a terminal disease. There's no cure. What are you supposed to do as the patient? How are you supposed to find hope? How are you supposed to get on with your life and live? The rates of progression are totally variable. You have no idea how much longer you're going to be around, but guess what? Nobody does. So what do you do? And I've just become fascinated by stories of spontaneous remission stories, there's a book by Jeff Rediger, Dr. Rediger called Cured, studying Spontaneous Remissions. You can read Dying to Be Me by Anita Moorjani and hear about her near-death experience having survived stage four lymphoma. There are 61 known reversals of ALS, non-genetic ALS studied of all places at Duke University by Dr. Richard Bedlack.
He's the man who has created ALS Untangled, which is a very important resource for people and their families dealing with the disease. And I've spoken to a number of the incredible humans that have... To be an ALS reversal, Dr. Bedlack will tell you, it means you meet the published criteria for having the disease and then regain some if not all of your function. The four-minute mile has been run. And so why can't I do it? And that's the level of commitment I have to reversing. I used to say beating ALS, but I think it's the wrong verb. It's healing.

Dr. Correa:
Now, you've been sharing a lot of your story and working to create greater awareness around ALS and advocacy for the community. And part of this has been a project called The Impossible Dream. Can you tell us a little bit more about that?

Aaron Lazar:
Well, yeah. So when I was in grad school in Cincinnati, I had an impossible dream to become a professional actor. That was my childhood dream. And that dream started to come true, ironically, as I played Don Quixote in the musical, The Man of La Mancha, and performed the big 11 o'clock number, The Impossible Dream to critics and agents from New York and was getting standing ovations. And I remember standing off-stage at the end of the show crying because I had this profound realization that my impossible dream was coming true. And I really had no idea what impossible really meant. And 23 years later, having been living with ALS for over a year at that point, well, almost two years, I was doing a concert in New York at 54 Below, which if you've never been, Doc, check it out, great cabaret space. I needed a song for the set. My great music director, Luke Frazier and the American Pops happened to have The Impossible Dream charts with them.
And I was like, "Hey, do you guys have The Impossible Dream?" He was like, "Yeah, we actually have that song." I was like, "Well, I haven't sung it in 23 years. Let's go for it." And I sang the song that night, and as I'm singing it, I go, "Oh wow," this song, there's something about the lyrics to dream the impossible dream, to fight the unbeatable foe, to bear with unbearable sorrow, to run where the brave dare not go. This is my quest to follow that star no matter how hopeless, no matter how far, the lyrics just bowled me over. And I spent the next six months writing a Ted Talk basically on my story and my journey and singing that song throughout. And then we started performing it in people's living rooms. Cut to last month, I was a keynote speaker at BIO, one of the biggest biotech conferences in the world, speaking to over 10,000 people.
So the message has gotten there. You can go to my website, please if you have any interest in booking me and hearing more about The Impossible Dream. But then when I publicly announced, a friend of mine asked me if I wanted to make an album, and he runs a production company that produces albums. And I said, "Sure." And so here we are. The album is called Impossible Dream. It just came out. I'm thrilled that you guys can get it streaming anywhere and everywhere. Check out Impossible Dream album on Instagram, and it's duets with eight of the biggest stars in the world. It's me and Josh Groban, Leslie Odom Jr. Kelli O'Hara. And the title track is The Impossible Dream, but it's We Are the World style with 50 plus stars, Kristin Chenoweth, Lin-Manuel Miranda, Sting.

Dr. Correa:
Wow.

Aaron Lazar:
And it's an anthem. It's an anthem of hope and resilience and belief in the face of whatever adversity you might be facing. And I'm proud to say that my kids singing the chorus on it. And my high school music teacher who got me started singing in choir, her and her husband are on it, my parents are on it, my brother and sister are on it. So it's all these stars, and then it's all these family and friends. And I hope you get a chance to buy the album and inspire yourself, inspire anybody who you think might need it.

Dr. Correa:
And Aaron, I'm wondering, as you think of the messages about health that you give to your kids and to the many other people out there who are just trying to find better ways to live healthier lives, what do you say to them?

Aaron Lazar:
I think balance is a key word. And I never rested before. I went from the work hustle to the home grind to if I had any spare time, let me get to the gym. And I wasn't really able to just enjoy sitting on the sofa and watching a movie with my family. I didn't love myself enough to love my life and to love life for whatever it was. And so be easier on yourself, be kinder to yourself. If I could go back and do it again, I would've done it a little bit slower with a lot more self-love and self-care and more patience and all those things. But for me, it took this thing for me to learn that. And I wish that wasn't true, but as I say at the end of my talks, whenever I give a speech somewhere, I wish I could have learned all this without ALS. Maybe you can.

Dr. Correa:
Well, thank you, Aaron, for bringing to us your own message of kindness to yourself and inspiring us with your own impossible dream.

Aaron Lazar:
I appreciate the opportunity to have the conversation, and I appreciate everybody who's listening.

Dr. Correa:
Can't get enough of the Brain & Life Podcast, keep the conversation going on social media when you follow @neurodrcorrea and @brainandlifemag or visit brainandlife.org. Welcome back or welcome to the Brain & Life Podcast. And today, I'm glad to continue our discussion that we just started with Aaron about his own experience with ALS. And welcome back, a previous expert and guest. Dr. Bedlack is a neurologist and nerve and muscle specialist with a special interest in understanding the needs of individuals and families living with ALS, working at Duke University School of Medicine. There at Duke, he's the director of the Duke ALS Clinic. Some of you, as I mentioned, may have heard him on our previous episode with Brooke Eby, and we are glad to welcome him back to the Brain & Life Podcast. Rick, thank you so much for joining us again today.

Dr. Bedlack:
Daniel, it's a pleasure to be with you.

Dr. Correa:
So I wanted to pick up, we start off the episodes often or these interviews learning a little bit more about you. Last time, we got to hear some about you personally. I wanted to touch on something else that's unique about your own self and that you bring to the bedside and office, your style. So tell us about the importance that you feel of sharing and expressing yourself in your way at work and with your patients.

Dr. Bedlack:
I think it's huge, Daniel. So the longer I work in this field, and it's been 23 years now, 5,000 families that I've interacted with. The more I believe hope is probably the most important thing that we can do for people with ALS and other neurodegenerative diseases. I mean, until the day comes when we have truly effective therapies, I think hope is more than just an emotion or a coping strategy. I've come to think of it as a treatment. If you look across almost every other disease where this has been studied, cancer and other sorts of terminal illnesses, CHF, severe strokes, people that are more hopeful do better medically, they've got better quality of life, lower symptom burden, lower risk of hospitalization, longer survival. And so I've come to believe that an ALS doctor needs to find a way to provide hope. And I've started to ask myself, how can I be the best hope giver? Well, I think it starts with, for me, what are my resources for staying positive? It's a tough time in the world right now.
It's a tough time in medicine. So much of it is driven by money, which is not what I'm interested in at all. And so I've got to say, how do I surround myself with things that bring me joy so that I can stay resilient? And one of the things that's brought me joy since I was a kid is my wardrobe. It's not great today, I'm just wearing a black sweater because it's cold here. But most of the time when I go to clinic and see patients, I'm in something that's bright and colorful and fun. And very often there's been some sort of a story behind the thing that I'm wearing. More and more, I'm working with designers on pieces that either celebrate lessons I've learned from people with ALS or celebrate families that have helped me on my mission to end ALS. And it brings me a lot of positivity and sets the table.
And then I think carefully when I go into the room about the words I choose, I would never put an expiration date on someone, look at them the first time I see them and tell them, "You got ALS, you got two to three years to live." It's not accurate. How do you know that when you see someone for the first time? There's a ton of variability in this disease. So why box someone in with an expiration date like that? Leave them open-ended, leave them a chance to be hopeful that they could live a lot longer, which is real. I'm always careful to stress the things we can do. I'm always careful to talk at the end of the visit about the research that we're doing and how people can get involved because I think that that's a really important source of hope for me, but also for patients and families.
And yeah, I mean, I always ask my patients now, tell me what things you're hopeful about, and you might expect that everyone's going to write down the same thing that they want to be healed. Very rarely does someone write that when I ask them to write these things down, it's very commonly they'll say things like, "I'm hopeful that Dr. Bedlack will have a solution for this pain, or I'm hopeful that I'll be able to attend my grandson's graduation. Or I'm hopeful that I'll be able to go to my brother's record release party. Or I'm hopeful that Bedlack will have some new experimental product I can try." Guess what? Those are all things I can help them realize with my team. So it helps us to personalize the visit too.

Dr. Correa:
So I think showing them in ways the things that matter to you helps you listen to what matters most to them?

Dr. Bedlack:
Exactly. Yeah.

Dr. Correa:
That's great. And great to be able to continue our discussion and our message of hope through Aaron's own message and story carries through that as we continue our discussion. Some of our listeners, although we've had several episodes discussing the topic of ALS and living with ALS might be new to the topic coming to this episode. So just briefly, how would you describe to a new person coming to your office or just recently diagnosed and to their family, what is ALS?

Dr. Bedlack:
Daniel, it's defined as a degenerative disease that most obviously affects a part of the body called motor neurons. And motor neurons are kind of like wires. They connect the front of your brain where you make decisions to your muscles that carry out your actions. So as this disease progresses, people know what they want to do, but they can't get the message to the muscles. And so unfortunately, most people will experience a loss of ability to walk, stand, transfer, feed themselves, dress themselves, eventually speak, swallow, and breathe. I think the impact of this disease is really best understood in the words of one of my patients, which I'll never forget.
She said, "This disease is kind of like living in a box, every day, I know it's going to get a little smaller, it's going to further restrict what I can do, and one day, it's going to get so small and tight that it's going to suffocate me." And I still get the goosebumps after all these years. It still, without a doubt to me, the worst disease I've ever come in contact with. And I mean, number one thing on my bucket list is to get rid of this disease. In the meantime, I'm trying to keep people as positive and hopeful and make their lives as good as they can be.

Dr. Correa:
And for our listeners, in each of the conditions that we highlight in our episodes, we try to work through a series of background and information, not just what is the condition, it's treatments research, but living with it and in the perspective of caregivers. So if you want more background and context in ALS, I'd say finish the episode definitely. But go back and check out some of our past episodes with John Driskell Hopkins, Brian Wallach, Brooke Eby, Lorri Carey, and other episodes on ALS so that you can learn more about the specifics, some of the research that's going on, advocacy work that's going on within ALS. We're continuing the discussion that we've had from those episodes now with Dr. Bedlack. So Rick, we've talked about in interviews with other individuals in the community, you of course have worked with over 5,000 individuals in the community. What has been the variety of life courses and progress that you've seen within the community of patients living with ALS? Because we have seen it's unique to each person and individual.

Dr. Bedlack:
Well, I'm glad that you recognize that. And again, I think that's why we have to be careful about presenting a homogenized version of this, when we sit down to tell someone this is what they have, it can go in a lot of different directions. I mean, unfortunately, I have seen people devastated by this disease in every way imaginable. But I've also seen the complete opposite on the spectrum. I've seen people who beat the disease. And I would say there's different ways of beating it. Very rarely I see people beat it physically. So there are a handful of people, now I know of 62 who meet diagnostic criteria for ALS, progress to where they're disabled, and then suddenly recover. Some most or all of their lost motor function, I call these ALS reversals. I just published a really interesting finding on the genetics of these people in the journal Neurology a couple of months ago.
But I'm studying these folks in the hopes that I can understand how this happens and someday maybe make it happen more often. But again, that's quite rare. It's more common, thankfully, that people beat the disease spiritually. In all the names that you mentioned that you've had on previous podcasts, including this one where we're talking about Aaron, these are all people who are beating the disease spiritually by not letting it change the best parts of them. They may be getting weaker on the outside, but the more important stuff that's on the inside, that's as good or better than it's ever been. I mean, listen to that album that Aaron just put out. It's so beautiful and it's so joyful in spite of the fact that he's weaker now than he was on the outside. His music is as amazing as it's ever been.

Dr. Correa:
I completely agree. I think each of those stories have enriched my own life hearing from them and to help them in their ways of advocating and supporting the community. So unfortunately, and I want to get to our discussion on ALS reversals and learn more about that from you. And I know our listeners hearing that want to know more. But I wanted to start off with, there remains no curative treatment and many medications have failed in the development process. Where are we in moving forward with a treatment that could modify the condition of ALS or provide even a hopeful cure?

Dr. Bedlack:
Daniel, I would say we have a lot of little things that add up to really improving quality of life for people with the disease and probably extending life too. So the drug that we have that clearly does work to slow the disease down is really is all, it's been around 30 years. It's not a blockbuster, but it does slow it down for people that are trying to do everything they can to slow it down and live the longest possible life. I think it makes sense. But I think the drug that excites me the most, because I think it's the tip of the iceberg in terms of where we're going, is the newest kid on the block, and that's tofersen, also known as Qalsody. This is an antisense oligonucleotide that is only for one very small subset of ALS. It's for people who have their disease because of a genetic mutation in something called SOD1.
So we understand this form of ALS better than any other. We know how the SOD1 mutations cause disease. They do it through the creation of a protein that gains a new toxic function, also called SOD1. And therefore, we understand exactly what we need to do to treat these people. We need to knock down as much of that protein as we can, which is what an antisense oligonucleotide does. And so this drug is exciting because it's the first time we've really known what we were doing in a clinical trial and also, because the FDA, I think, was very smart in how they approve this drug. So in the past, they've only approved drugs that showed some clinical benefit. It can be very difficult in a disease like ALS to show a clinical benefit, especially when you're talking about a rare subset of the disease. Again, only about 1% of people with ALS have this form, it'd be really hard to do a large clinical trial where there's only 300 people in the whole country with this form of the disease.
And so you need to be creative in terms of how you're going to look for an effect. And here they said, "We want to see a pharmacodynamic effect. We want to see that you've knocked down this SOD1 protein, but show us a biomarker that shows that you're preserving motor neurons." And so they had one, neurofilament-light chain, and they knocked it down so robustly that the FDA was confident there would be future clinical benefits. Even though at the end of the clinical trial there were trends but not statistically significant benefits on any clinical measure. They gave it something called an accelerated approval, meaning we think this works, but we want to see more data and more data is now pouring in. So we got this in the hands of patients, and we're seeing now in people that have been on this for in some cases years, most of them are stabilizing.
Some of them are even regaining loss function. That's a meaningful treatment effect when you can stop or reverse the progression of the disease. That's the bar that we should be setting for future therapies with this disease. And I don't think we can get there until we understand all the different subsets better. There's 40 different genes that comprise genetic ALS. SOD is just one of them. Many of the others we know about, but we don't fully understand how they cause disease. And that's only 10%, altogether, that adds up to only 10% of cases. 90% don't have an obvious genetic mutation that's called sporadic ALS. Like we're just shooting in the dark in our clinical trials trying to address targets in sporadic ALS. We're guessing.
I mean, I think as we get more biomarkers, as we have a better understanding of what causes subsets of sporadic ALS, we'll see results that are much more meaningful. We'll be able to stop or reverse progression in more subsets. I mean, think back 40, 50 years probably before you were born, Daniel, when people were talking about a cure for cancer. Well, now we realize that's silly. Cancer's different. There's not be one cure for all cancer, but we're finding cures for subsets of cancer. And I think that's where we're going to be going with ALS as we understand subsets better. We can talk about more drugs like tofersen that are home runs for subsets of ALS.

Dr. Correa:
I'm touched that you think I'm younger than 40. So I wanted to get your reflection on. So the Qalsody or tofersen has gone through this accelerated process, and it's been a hopeful story with the data that we're getting from that. But similarly, within the ALS community, Amylyx went through an accelerated process and unfortunately the later data started to show that it just wasn't really showing the efficacy that it should. How would you discuss new medications that are coming down the way when they go through this process with individuals? Of course, there's the specifics of the data that we have for whatever that new medicine is, but in the context of this process being advocated for by the community greatly, both within cancer, dementias and ALS, but this mixed data that the community is learning from over time.

Dr. Bedlack:
Well, Daniel, I would say the Amylyx story was not a story of failure. It was a story of how an accelerated approval is supposed to work. So we have this horrible disease where, yes, we have a lot of small things that we can do, but we don't really have a significantly effective therapy for most people with this disease. So there's a huge unmet need. So if a drug comes along where a small trial has shown what appears to be a meaningful benefit, and recognizing that we can't always trust the results of a small phase two trial, we have to replicate it. You have two options.
One is you can sit on your hands and say, "Well, we're not going to do anything for three more years until we get the results of the phase three trial, and we can be absolutely sure." Now, if that trial shows that it's a win, it's a blockbuster, what do you go back and tell all those patients and families whose loved ones are more disabled and in some cases dead when they didn't need to be? Let's get the drug out there in the hands of people that want it, people that are willing to take a risk of some uncertainty, but let's not forget to keep studying it.

Dr. Correa:
Yeah, I agree. We need more incentive for the pharmaceutical companies to continue research in these agents, and it's been helpful to see this process moving forward, and I'm glad to hear that, at least from your perspective and communication with the community that you provide encouragement in this. Of course, it's going to lead to some medications that don't show efficacy, but we need this kind of work to move forward. If not, we end up with so many other medicines that we need more data on, but it's left to the VA or other institutions to do the studies and not the company.

Dr. Bedlack:
Yeah, I mean, we could talk about the drug approval process and drug companies. We could talk for hours about this.

Dr. Correa:
It's probably more interesting to us. But let's continue what Aaron mentioned. He mentioned how he came to learn about your work because you have spoken and mentioned about studies of cases of ALS reversals. So many individuals want to hear and learn more about that. ALS doesn't have a specific cure as we've talked about. So what does an ALS reversal mean?

Dr. Bedlack:
There have been cases reported in the literature dating all the way back to the 1960s of people that appeared to have ALS, progressed for a while, in many cases to where they were disabled and then recovered most or all of their lost motor function. And many times the conclusion from those case reports is, I must've been wrong, and I discharged the patient from clinic. And as I started to understand that this literature was out there, I was like, "What in the world? Why has nobody tried to put all these cases together into a database and study the heck out of them?" I mean, I don't know what these are. I mean, it's possible there's some other disease that looks just like ALS, but it's self-limited, but isn't it also possible that this really is ALS and that there's something different about these people or something that they took that allowed them to recover from the disease?
Look at the HIV literature. We've known since the 1980s that there were a group of people that got the virus, you could measure it in their blood, but never progressed onto AIDS even though they took no highly active antiretroviral therapy. They're called elite controllers. And it used to be that people just shrugged their shoulders and said, "I don't know. I don't know what's going on with those folks." And then somebody said, "Let's put them all in the same database. Let's study them." And they found that many of those folks had the same genetic mutation. It was in a gene called CCR5. And so they immediately said, "What does that have to do with HIV?" Wow, look at this. It's a protein in the surface of cells that HIV needs to get in, immediately, a drug company built a drug that blocked that pathway called Maraviroc, and it seems to really help everybody with HIV.
So there is a precedent for learning from these extreme outliers within a disease, and that's what I'm hoping will happen with these studies of ALS reversals. We did find something interesting recently. We found this mutation that's present in about a third of the ALS reversals. It seems to be in a gene that controls the expression of a protein called insulin-like growth factor BP-7, IGFBP-7. From other databases, we predict that this mutation will reduce the expression of the IGFBP-7 protein that allows us to come up with a hypothesis. How could this lead to an ALS reversal? Well, IGFBP-7 does a lot of stuff, but one of the things it does is it blocks the interaction between the growth factor, IGF-1, and motor neurons. So with less of it around, that interaction can be more robust. Motor neurons can be more resilient.
Maybe people get a milder form of ALS one that they don't have to die from, that they can actually recover from. It's just a theory, but we've got follow-up studies underway with a group called ALS TDI, and we plan to present the results of those studies in November. ALS TDI will be doing a public webinar that I'll be part of. And when we put all that data together, we'll know what our next steps are. We'll know whether we're going to drop everything and do a clinical trial, trying to knock down IGFBP-7, or whether this doesn't look as important as we thought it was. But to me right now today, I'm incredibly exciting that we did find something that many of these ALS reversals have that's different from people with ALS that does not recover.

Dr. Correa:
That's incredibly interesting and helpful. And I'm wondering, within this community of 62 cases, do any of them have the genetic form of SOD1 or these are all as we would describe as sporadic?

Dr. Bedlack:
So amongst the ones we could test, because again, some of them are gone. I mean, some of them were in a case report from the 1960s, so we only have what's in the case report as far as information. We can't find that person. We can't get samples from them. But amongst the ones that we could genotype, which I believe we were able to genotype 22 of these folks, there was one that had an ALS-causing mutation. It was not SOD1 though, it was a more rare disease-causing mutation. So that's slightly lower again than 10%, but it's still, again, I think it argues that there are some people who not only meet clinical criteria for ALS, but also have an ALS-causing gene.
So if someone stands up at a meeting and says, "Well, all these people just had ALS mimics, none of them actually had ALS." Well, the two arguments I would make are there's a published set of criteria for making an ALS diagnosis. They all met that, and one of them even had an ALS-causing genetic mutation. Don't you think that would be a strange coincidence that they met all the published criteria and had a disease-causing mutation and they had a mimic of ALS? Gets to be kind of strange. I don't think that was a coincidence. I think that at least some of these people really have ALS.

Dr. Correa:
And within that group that you've been able to take a look at other similarities, it's still a small group and a number, and we've talked about on this podcast at times until you have larger numbers, some of the statistics that we'd like to see become very difficult to really clearly prove and show. But are there similarities in many of the other aspects about the timing of their condition, the age of onset, other things that seem to be similar about these cases and maybe in your opinion or perspective, different from some of the other cases that you've managed and treated at your center?

Dr. Bedlack:
There's not really a glaring difference. I would say there's some subtle differences. So the group of 62 ALS reversals, they're slightly more likely to be Caucasian. They're slightly more likely to be men. They're slightly younger than people with typically progressive ALS. On average, they seem to progress a little faster before they start to recover from ALS, which is really strange. I mean, we've looked at the things that they take, the products that they take. There are a few things that are different. Reversals were more likely to take a product called curcumin, a supplement, which led me to devote three years to doing a clinical trial of a potent form of curcumin to see if that could reverse ALS and it didn't.
Where I am today is I think that just like ALS itself, there's probably not going to be one single explanation for why someone might recover from ALS. Maybe some of these cases are mimics, maybe some of these cases recovered because of something that was purely endogenous, like this mutation that controls IGFBP-7. Maybe some of these people found just the right medication or supplement for their particular version of ALS. I don't believe that there's ever going to be one drug or supplement that reverses all ALS, but what if there is some drug or supplement that interacts with a biological pathway so that in a subset you can have a cure?

Dr. Correa:
Wow. We can be hopeful as we are with all efforts and initiatives towards personalized medicine, that that effort at least will move forward. Now, I want to know, you mentioned that among the similarities in these 62 ALS reversal cases that many of them are men, many of them are white. I have my own interpretation, but do you think that that suggests that a greater majority of men or white individuals are more likely to slow down or stop or have a reversal? Or why is that something that seems to come out at least in that group?

Dr. Bedlack:
Well, for one thing, ALS is more common in Caucasians. ALS is more common in men. So it would be really weird if the demographics of reversals were very different than the demographics of ALS itself. So I think there's that. The other thing that's interesting is that this single-nucleotide polymorphism, this mutation in this gene that we found, it's very much tied to ethnicity, so it's much rarer in Caucasians than it is in people from Africa or Asia, people from Africa or Asia, it's much more common to see this polymorphism just naturally occurring. And it does actually make me scratch my head and think, is that why these people are less likely to get ALS because they have a higher frequency of the SNP that controls the levels of IGFBP-7. Again, it's just a theory, but I don't think anyone's ever previously had a theory as to why ALS is so much less common in non-Caucasians.

Dr. Correa:
The process of care and support for individuals and their families with ALS is a very resource-intensive process. Even the challenge of really making a clear diagnosis and ruling out other things that might be mimickers can be significantly resource-intensive. Do you think that has impacted why we see fewer numbers or smaller numbers of ALS in other countries and in other areas around the world?

Dr. Bedlack:
I mean, it's a great question. It's impossible to know for sure. I mean, you can't know about people who are not coming to medical attention, but the disease is so disabling, so dramatic. It's hard to believe there could be a lot of people out there who are undiagnosed. I feel like there is something different about these different ethnicities in terms of their risk for ALS. We just don't know for sure what it is. And IGFBP-7 is a theory. I haven't heard anyone else propose a theory before, but there's no doubt that the care of ALS is very different in different parts of the world, and that's heartbreaking. I can't tell you the number of emails I get from all over the world every day from people that are in some place that just doesn't have any interest in it, any knowledge of it, any multidisciplinary clinics, any clinical trials, any hope. I wish there was a way to be able to connect with all these people to at least get them that basic level of care and at least be able to inject some hope into their lives.

Dr. Correa:
I hope that also for them, and that's an area of improvement that we can do for the burden of many different neurologic diseases around the world. And as you take this message of hope, the work that you're doing to many different community and advocacy groups within the ALS community, how do you think the discussion about ALS reversals helps those living with ALS and their caregivers?

Dr. Bedlack:
I think it reminds people that the course of this disease can be very different in different people. I mean, I'm sad to say that the vast majority of people that come to see me, they say exactly this, "When we were told we had this, we were told, you have two to three years to live. Go home and get your affairs in order." And I even hear people say, "We asked our doctor about hope and they were told hope is not a strategy." Well, I mean, I don't know who utters these words to people. Whoever it is has obviously never been personally impacted by these diseases and hasn't read the literature on the course of ALS nor the importance of hope across different diseases.
I think these are the exact opposite of the things that we should be saying to people. And I think just putting that out there for people who maybe are going to a clinic that's not as good at talking about variability or hope allows more people to see it, allows more people to have the hope that is so important and hopefully is allowing them to do better with the disease than they would've done otherwise.

Dr. Correa:
Now, thinking of the little naysayer standing up in the back of the room, sometimes even an individual living with ALS, one of their family members, that's just very data or empirically minded. Do you think that a discussion of hope and a discussion of ALS reversals potentially takes away from the mental preparation that they and their family have to take on and the path of their condition?

Dr. Bedlack:
Such a great question, and I get this all the time from those colleagues who are not fans of my approach is that I'm giving people false hope and I'm preventing them from preparing for the disease. And that's completely wrong. I would invite anyone to come and watch what I do. I'm not lying to people. I mean, I tell them it's a disabling and often life-shortening disease. And as we get to different points in the disease, I tell them, "Hey, there's some things coming up that we need to talk about." But I present it as let's have a plan A and a plan B, okay? So plan A is we try the next experimental thing. We hope to slow stop or reverse ALS. I'll get you something that we can try either through a trial or expanded access or through an ALS untangled supplement that I have some confidence in.
But you have to help me with a plan B. Like if you're swallowing keeps getting worse, we need to think about a feeding tube. If your breathing keeps getting worse, we need to think about a ventilator, have you thought about if this really got worse, even with non-invasive ventilation? Would you want a tracheostomy? Would you want invasive ventilation? Let's talk about what that looks like. Is that right for you? So I would argue that the people in my clinic probably have a higher frequency of having made these decisions at an earlier point in the disease than other clinics. So it is possible to keep people hopeful, but also help guide them to make advanced care plans throughout the disease.

Dr. Correa:
You're empowering them to be able to have the mental bandwidth to make those decisions and think about that, and have that discussion and not just be lost in the mire of darkness. And Aaron talks about how he has been on his own spiritual and physical journey with his condition and with his family. How do you relate and connect and help others through their process? They're coming to you with such a disabling condition and you're speaking to them from a perspective of health and wellness that you don't imagine how a caregiver or a person might first come to you and think, how could you possibly understand this situation?

Dr. Bedlack:
Yeah, no, I mean, I think that's where it starts. It starts with understanding who this person is, what's important to them and their family, and trying to figure out how we can maintain those important parts of their life. ALS does not have to define someone's life. ALS is a small part of who my patients are. I mean, I'm trying to take care of the rest of them. Well, we try to figure out how to stop or reverse ALS. I'm trying to figure out how can I keep them doing the things they love, making music, traveling, playing a particular sport, doing things with their kids?
I mean, these are all things that are so much more important in a person's life than the diagnosis of ALS. So that's the job of me and my team to understand who these people are and try to help them hold on to the best parts of them. Like we talked about, beating the disease spiritually, that's possible for everyone, but you have to help us understand what does that mean for you? What does that look like for you? As part of why we ask the questions, what do you hopeful about? Because it shows us what is important in your life today that we need to try to work on together.

Dr. Correa:
Well, Rick, thank you so much for not just helping amplify a message of hope and a broader perspective on management of the condition for your own colleagues, but being there for the community living with ALS, and giving them hope and helping us learn more from your own experience and from the experience of some of these ALS reversals.

Dr. Bedlack:
Well, thank you so much for having me back on. And if you haven't heard Aaron's album, I highly recommend it. It's one of those, it's not only beautiful, but it's incredibly hopeful, and we're trying to get one of his songs into a movie that I'm making about the way that I try to promote positivity and hope. The movie's the same name as my Instagram handle, which is Stitching Strength. And I mean, some of the songs I love on his album, When You Believe, Fight The Dragons, Never Walk Alone, and The Impossible Dream, are just all beautiful, hopeful songs that I think resonate with me and my team.

Dr. Correa:
And we were so glad that Aaron shared some of the music with us for this podcast. We had a clip at the intro, and now as you listen at the end of the episode, you'll hear the full song.

Dr. Bedlack:
Awesome.

MUSIC:
When you're down...

Dr. Correa:
Thank you again for joining us today on the Brain & Life Podcast. Follow and subscribe to this podcast so you don't miss our weekly episodes. You can also sign up to receive the Brain and Life Magazine for free at brainandlife.org. Don't forget about Brain & Life en EspaÃ±ol.

Dr. Peters:
Also, for each episode, you can find out how to connect with our team and our guests along with great resources in our show notes. We love it when we hear your ideas or questions. You can send these in an email to blpodcast@brainandlife.org and leave us a message at (612)-928-6206.

Dr. Correa:
You can also find that information in our show notes, and you can follow Katy and me and the Brain and Life Magazine on any of your preferred social media channels. We're your host, Dr. Daniel Correa, connecting with you from New York City and online @neurodrcorrea.

Dr. Peters:
And Dr. Katy Peters, joining you from Durham, North Carolina and online @KatyPetersMdPhd.

Dr. Correa:
Most importantly, thank you and all of our community members that trust us with their health and everyone living with neurologic conditions.

Dr. Peters:
We hope together we can take steps to better brain health and each thrive with our own abilities every day.

Dr. Correa:
Before you start the next episode, we would appreciate if you could give us five stars and leave a review. This helps others find The Brain & Life Podcast. See you next week.

MUSIC:
When the doctors failed to heal you.
When no medicine chest can make you well.
When no counsel leads to comfort.
When there are no more lies they can tell.
When there's no, no information.
Oh, and the compass turns.
Oh, the compass turns between heaven and hell.
Just let your soul be your pilot.
Let your soul guide you.
He'll guide you well.
And your eyes turn towards the window pane.
To the lights upon the hill.
And the distance seems so strange to you now.
And the dark room seems so still.
Let your pain be my sorrow.
Let your tears be my tears too.
Let your courage be my model.
Know that the north you find will be true.
When there's no information.
And the compass turns to nowhere that you know well.
Let your soul be your pilot.
Let your soul guide you.
Let your soul guide you.
Let your soul guide you upon your way, your way.

Aaron Lazar on His ALS Journey and the Impossible Dream

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