The Power of a Rare Disease Community - Luke Rosen, Founder of KIF1A.org

Shiv Gaglani: Hi, I'm Shiv Gaglani and today on Raise the Line, our focus on rare diseases and conditions continues by welcoming another inspiring parent who's managing to not only care for their child but also advocate for other patients and their loved ones. I'm happy to welcome Luke Rosen, the founder and Board Chair of KIF1A.org, which is working to rapidly discover a treatment for KIF1A-associated neurological disorder -- or KAND -- a rare degenerative genetic disease which his daughter Susannah was diagnosed with in 2016. There's currently no cure or treatment for this condition. 

In his professional life, Luke has spent the past five years in patient and community engagement at Ovid Therapeutics, a biotech company focusing on rare neurological disorders. He's also had a career as a writer and actor appearing in shows such as Orange Is the New Black and the Unbreakable Kimmy Schmidt.

Before we get started, I'd like to thank Akiva Zablocki -- who folks may remember was on the podcast a couple of months ago talking about hyper IgM syndrome and his son, Idan -- for the introduction to Luke. So, Luke, thanks for taking the time to be with us today.

Luke Rosen: No, thank you, Shiv. It's such a pleasure and echoing a big thanks and shout out to Akiva who is somebody who I love and is so close to my heart.

Shiv: Agreed. That's one of the most gratifying parts about doing this focus on rare disorders or zebras, is meeting parents and patients like yourself and Akiva who also seem to know each other and have supported each other over the years.

Luke: Absolutely. I mean, we really take pages out of each other's books, or I certainly have for Akiva. You know, Idan and his whole family are, like I said, very close to our hearts. So, thanks to Akiva for making this introduction.

Shiv: Awesome. We're definitely gonna go into your and Susannah's story and KIF1A, but the first thing I know our audience would be interested in hearing more about is your professional background, and this whole acting and writing career. Can you tell us a bit about yourself first, and then we'll go into the other stuff?

Luke: Yeah, sure. Absolutely. Thanks for asking. For about twenty somewhat years, I was an actor and writer in New York primarily on film and television. I wrote some plays. People say it takes ten years to really kind of establish yourself and make a good living as an actor and to be constantly working. Well, it certainly did take that ten years. But after that, it was wonderful. I met my wife, and we had our oldest son Nat, who's just incredible. Nat used to come to set with me and hang out and was very much part of my life as an actor. And Susannah was born. Susannah -- actually, I'll send you the picture -- Susannah came to work with me one day, and was in this print ad with me for Xerox. I was holding her like a football and she was in my arms. They did the shot, and I was all over buses and magazines and airport jumbo screens. She was a member of the union before she was one year old. Susannah is in her own right a very wonderful actor. So, acting was a big part of my life.

When Susannah was born in 2016, we started noticing that something was happening and something was seriously wrong with her health. I was in the middle of writing a play called Over the Moon with Trains. We were in the middle of our workshop productions and were about to open. We were here in New York, and were about to open in England and I was traveling a lot. I'd be back and forth from California to New York and England sometimes. When I knew it was time to take a timeout from acting, I spoke with my agent and said that I was going to step back from it a little bit and we weren't quite sure what was going on. They were going to continue this play without me, which would ordinarily have been fine, but the play had had so much of Susannah and Nat and my family in it because it kind of transcended from what was happening in our real life into my work. I kind of hold that one close to my heart, kept it in my pocket, and haven't showed anybody that one.

So, I was kind of sitting and speaking with my wife, and we realized that we needed to do something to really help not just our kid, but kids who are out there with this disease, which at the time...we didn't know any, right? There are maybe twelve or fourteen that we could find -- and mostly in literature -- when Susannah was diagnosed. So, we set out to start a foundation and build a community and find more kids. I realized that that was a far more impactful endeavor than doing beer commercials around Superbowl time. That's when we made the decision to do that and the luckiest thing that happened was the first few families we met. 

Kat Atchley, who's the president of the foundation, is just an incredible person and had nonprofit experience and we were just very fortunate. I always think that leaders should surround themselves with people who are better than them. We were very fortunate to find people with skill sets that were helpful in really jumpstarting the foundation and preclinical work we're able to do. So, that's how we started the foundation.  

Shiv: That's fascinating. We're definitely gonna go into a couple of those threads here. But first, before we dive into it, how is she doing? 

Luke: Susannah is eight right now and she'll be nine in May. She's okay. You know, it's easy to say that default answer, "Oh, everything's okay," but it's really not. She's lost a lot of her vision, she's got hundreds of seizures at night and she's having difficulty walking. So, things are a little bit difficult at home. But thank goodness for science, because we really are on the brink of several things for hopefully the entire community. Susannah has been fortunate enough to just have started an experimental treatment thanks to a really amazing organization called n-Lorem. I'm not sure if you've heard of the n-Lorem Foundation, but they're really just wonderful people who set out to leave no kid behind because it's such a rare condition that a lot of traditional pharmaceutical companies, you know...there's no real market size. This organization was working with our physicians to not just find an experimental treatment for one person, but hopefully to scale it for the entire community. So, that's something that I'm excited about, both on a personal level and as a community leader too.

Shiv: I'm sure there's some hope there, which is great.  For our audience that probably has not heard of KAND or KIF1A, the gene itself, can you give us an overview of the condition and kind of what happens, how common it is, etc.?

Luke: Yeah, of course. Like I said, the community really galvanized together even though it was very small. Right now, five years later, we have approximately four hundred families around the world that we've identified and we've done that by advocating for next generation genomic sequencing and the right genetic tests for the kids. Often the kids are misdiagnosed with cerebral palsy or other severe diseases, like Rett syndrome or LGS is another disease. So, one of the things we've done is really gone out there and tried to make sure that the gene was recognized as a diagnosis, because it does have to be diagnosed with a molecular test, with a genetic test. You can't just kind of see a kid in the clinic and say, "Oh, that kid's got KIF1A." It's a very complex and heterogeneous disease. 

The disease itself was caused by a mutation in the KIF1A gene which is a molecular motor protein that's vital for brain function. It's a large gene. Our disease, as we find more people, is very heterogeneous. There's not just one mutation like some other diseases that you might know of, but there are multiple different mutations across the gene. And that heterogeneity isn't just in where the mutation is, but it causes different affects and then different presentations and different severity and progression of disease for the individuals who have those different mutations on the gene. For some, unfortunately, it's very tragic and it's a lethal disease before the age of five in some of those mutations. 

Other mutations, like Susannah's, are progressive over time. We do see the degeneration in her with her disease. The disease really is characterized by cerebral atrophy, so the brain is atrophic as time goes on; optic nerve atrophy, so that's where the vision loss comes in; and spastic paraplegia, which is basically lower limb specificity. So, lots of our kids are in wheelchairs and use walkers and as they get older, it worsens. I'm sure I'm forgetting some of the constellation of medical complexities that come along with this disease. 

One of the most difficult parts is there's significant hereditary neuropathy, we call it, which is neuropathic pain. The nerves in the body are degenerating, so there's a toxic protein that these mutations cause and that causes nerves in the hands and feet to slowly die or rapidly die depending on where your mutation is. That's very painful, a lot of times, Susannah will wake up and say, “My hands are burning on the inside,” in her own way. Some of the kids are nonverbal. We’re fortunate that Susannah has speech. You have to be well versed in speaking “Susannah.” It's like a different language, but we understand. So, the hereditary neuropathy is something that we're dealing with now and hoping to address. I know a lot of people in our community are too. Those are just a few of the mysteries and the medical complexities that people with KAND deal with.

Shiv: I mean, the heterogeneity makes it so difficult, not only because it's such a rare condition, but also the presentation then is so different. One of the big challenges of all rare disease communities is getting big enough numbers for clinical trials to understand it. So, tell us about KIF1A.org. You started telling us about the evolution of it, but what are some of the top priorities you have now and what are you most proud of that it's done?

Luke: That's a great question. First and foremost, the thing that I'm most proud of is that the organization has galvanized such a strong community. Everybody's very active in the community. There's not one family I know that doesn't play a significant role in what we do between just dialogue and support, all the way through our mission which is to really drive science to a therapeutic for families. That's pretty incredible that everyone plays a real part. 

Something else that I'm really proud of and thankful for is our collaboration at Columbia, which is a commonality that Akiva Zablocki I have. We being in New York, our family ended up at Columbia. That's where our kids were born, that's where if broke my arm I'd go to that ER. It's just around the corner. So, we landed in Dr. Wendy Chung's office who's the Chief of Genetics at Columbia. We just happened to be fortunate enough to be in a place where there was somebody who could interpret the results of the diagnosis, and also is an incredible researcher and physician. 

When we started the foundation, it was quite obvious that to centralize all of our resources and all of the families around this preclinical program at Columbia was the right thing to do. Right now, we have something called the KOALA study. Every good study needs a good acronym, right? So, it's called KIF1A Outcome Measures, Assessments, Longitudinal, and Endpoints - KOALA. In rare diseases, one of the major problems is that the outcome measures and endpoints that regulators and other people use are really antiquated. I mean, they've been around for far longer than our disease has, so it's hard to find measures and tools to measure that are standardized that are appropriate for our disease. By that, I really mean that Susannah can sometimes have hundreds of seizures at night, and if an endpoint is a 50% reduction in seizure...well, that's great, but two fewer seizures would be huge for us. Just ten more steps would be great, not getting up and running a marathon and things like that. 

So, the study aims to fly or travel all the families, both international and domestic, to our center of excellence at Columbia. All the families have clinic visits, answer certain survey questions and go through an assessment for the various domains that are relevant in our disease. The hope there is that we'll have a real understanding of the disease, but also have a way to measure change and to understand what really matters for every family across the heterogeneous disease that we have.

Shiv: That's really exciting and hopefully a good model for diseases like KAND that have such heterogeneity. It reminds me of something John Crowley, who I'm sure you know, told me on the podcast as well about the endpoints. We were talking about his daughter, Megan, and his other son who have Pompe Disease. Quality of life improved significantly for these patients and their family members. If you can just get, as you said, instead of 100 seizures at night, just ninety-eight. Right? And obviously getting to statistical significance is clearly important if we're going to be able to find and approve drugs or treatments for these conditions. However, the lived experiences are really important for these families. So, that's a really interesting study. I'm glad to hear.

Luke: I think small change is epic for rare disease families. Incremental change even means a lot. John Crowley is somebody who has been a guide and a mentor for me since Susannah was first diagnosed, and his daughter Megan is a great inspiration and leader for young girls like Susannah.

Shiv: That's awesome. Yeah, a great person, great family and again, that's one reason we love covering this because of so many heroic and inspirational stories. Going into key priorities, KOALA is a really interesting study to be aware of. I think there's also a mouse model and trying to get cell lines to test potential therapies. Do you want to talk a bit about that?

Luke: Sure. One of the best moves we made was, with the help of the Chan Zuckerberg Initiative, we were able to resource a Chief Science Officer. I can barely get through what KAND is without crying or rambling. I was doing and Chekhov in some shitty East Village theatres, not at the lab learning science. So, we were able to hire our Chief Science Officer, who was one of the handful of people in the world really researching and working on the disease, and that's Dominique. 

One of the things that we learned about biotech is, you have to work non-sequentially. You can't waste time by crossing something off the list then going to the next, then going to the next. We kind of try to take all these shots on goal at the same time and so along with the KOALA study, we're also certainly working on finding the right animal models, but most importantly, getting cell lines from all the families. 

So, our partners at Columbia work really, really closely with Cat Lutz and the people at the Jackson Laboratory who are also just wonderful people. The Jackson Laboratory is another nonprofit but with incredible scientists who really work on developing disease models, and not just in mice, but isogenic cell lines and other things like that. So, with the folks at Jax, we were able to identify a mouse model that mirrored some of the lower limb spasticity of the disease, which was really critical in making progress and understanding and being able to test therapeutics on that animal model. 

But we're not aiming to find treatments for mice, so it was really important for all of our families to be educated and that's another great thing about our foundation. Dominique, who's our CSO, is the person who focuses on scientific communications and SciComms is huge. So, we put together an initiative to make sure that all the families knew how important it was to give blood, not just for analysis, but to create human-derived cell lines. Because of the heterogeneity of our disease, we need not just one or two people to give blood to make cell lines, we needed to get as many of our families to give those samples as possible so we can make cell lines and be able to mirror the disease in a dish, as I say.

We do it in what I think is a very innovative way and practical way. I think that innovation these days is often just being completely practical, and sitting down and having coffee with somebody instead of developing an app, maybe. I don't know. So, we have big family and scientific conferences. Our last one in person was 2019. We've done virtual since then. But our incredible president who I mentioned, Kat Atchley, she really drives those and there's a great convergence of community and science. At the conference we had a lot of people presenting, we had a lot of community support events and activities, and we had a phlebotomist taking blood from all the families. It's constantly a community and support driven foundation with very much a scientific element to it. I think without both of those, you can't get to a treatment fast enough. So hopefully, we're on the right path, and we're doing lots of different things at the same time from investigating genetic based therapies to screening small molecules to really, really digging in and understanding what matters most to our communities.

Shiv: That makes perfect sense. I like that analogy of doing things in parallel and taking multiple shots on goal. Plus, going back to the basics. So much of this is that awareness and education and trying to get families to know why you need to donate blood and make it super easy for them by doing it when they're at the conference.  I was wondering if you were going to say, maybe, to get into the line for dinner, pizza or cookies or whatever, you'd have to donate blood to get there which would be a perfectly reasonable thing to do. (laughs)

Luke: (laughs)So we thought of that. We actually thought of doing it so when you check in to get your badge, the phlebotomist will be the person who's giving the badge. We decided that education was a better route than you know, forced...(laughs)

Shiv: forced blood draw (laughs). I'm also glad you mentioned Chan Zuckerberg. We actually have Tania Simoncelli coming on the podcast and a couple of weeks.

Luke: I just have to say Tania is in many ways responsible for what success we’ve had and where we are right now as an organization. Tania is an incredible guide for us and also is incredible at putting people together to drive things forward faster. Tania is one of our champions. I'm forever thankful to Tania, so I can't wait to hear that one. She's amazing.

Shiv: Totally, and she has a great team. They have Heidi Bjornson‐Pennell, who herself has two children with a rare disease, and then I was introduced to Tania by David Fajgenbaum because both Tania and I are on his Every Cure advisory group. So, great people. I'm glad to hear that CZI has been backing KIF1A.org.

Luke: Yeah, and talk about taking pages out of people's book. David is also a friend of mine. I think this is unique for rare disease where with other diseases people take great ownership of what they do, but certainly KIF1A.org -- and certainly the people that you just mentioned when somebody asks them how to do things, it's kind of like, "Here, look at our website, take it. Take whatever we've done as a community and try to apply it to your disease.” That's the case with David and Tania. David, obviously, has worked relentlessly to make things happen faster. In so many ways, he is not only transparent but sharing and loving and says, "Here, take it. This is the model that works, use it." So, we're forever grateful for community members and leaders like those.

Shiv: Absolutely. It takes multiple stakeholders getting involved, including the parents. The way you're speaking about KIF1A..if anybody tuned into this without knowing your background, they would think you're a researcher yourself because you know so much about the condition. You've had to learn. I'm curious on this point, since our audience primarily comprises current and future healthcare professionals, as well as researchers: what advice would you give them about being helpful? Like, think about some of your best and maybe worst experiences of the healthcare system in regards to KIF1A and how you as a rare disease family were dealt with. What’s some advice you'd like to give our audience about that?

Luke: Oh, what a question. I think that the advice really is to spend time to sit down and listen, and that listening doesn't happen nearly enough. We're very fortunate to have physicians who listen and who observe and who love our kids, who are like their extended family members. I mean, our physicians are constantly checking in and are very honest with us saying, "Look, we don't know much about this condition. The only way we're going to learn about it is to listen and learn what your routine is like.”  It takes a community to want to be able to share their stories, which is tremendously difficult. It's really hard to write about it, to talk about it. It's just exhausting and often excruciating to relive it. 

I think it’s really helpful when healthcare providers, when industry members, when people give the community a platform to tell their story -- just like you're doing -- and give the community a way to articulate things that the person looking in from the outside might not necessarily know or understand. It gets back to those outcome measures. I want people to know that if there's some way to get my daughter five or ten more steps so maybe she'll be able to make it to the bathroom without having to completely lose the routine of our day, that would be huge because that gets my son anxious and gets him late to school.

There are so many different elements, and siblings are remarkable, right? When people ask us to tell them about the seizures that Susannah has...yeah, sure I can tell you about the seizures she has and how my wife and I haven't slept in the same bed because one of us has to sleep with her. But the thing I think about when the clinician or anybody asks me about Suzannah's seizures, is the one time where I wasn't sleeping with her and my wife Sally was out of the house. Nat, Suzannah's brother, said "Let's have a slumber party." So, the kids got into bed and the three of us had this incredible, you know...any parent would love that moment where the kids fall asleep watching a movie on your shoulders. It was great. Long story short, I kind of snuck out of bed to get ready for the day. Then I heard a scream from our son who said, "Dad get in here. Something's going on with Susannah." She’d had a seizure and vomited and was aspirating and the reason that she didn't die was because her brother was there to save the day and to help. 

I think that knowledge that siblings go through that sort of thing is something that needs to be talked about when somebody says "Tell us about your child's epilepsy."  It's more than just a quick answer. It's a huge effect on not just the whole family, but friends and everything. So, I guess that's a way of saying that my advice would be to really ask questions, to really listen, to really spend the time and to be open. I think the best scientists and physicians are the people who are constantly learning.

Shiv: Certainly. I think that's great advice and really nuanced. We've done several of these interviews and no one shared that particular item about siblings. That's a really good thing to consider. No one is just a person in a vacuum. They are a person in a family unit, in a community, and so being able to consider those other aspects that make them who they are is critical.

Luke: Absolutely. That's so well said. On the on the research and science side, I think that engaging every single level of scientists, researchers and clinicians is huge. I mean as a foundation, everyone thinks about raising money and being able to resource things. I think the goals is to create a clinical trial-ready ecosystem, or create something where you can go to a company or a scientist or a lab and say, "We'll be your proof of concept, because we're so ready. We have a center of excellence that could be a clinical trial site right away. We can rapidly enroll. We can do all of these things that new technology and clinical trials need. " I think that's currency that is just as important as raising a million dollars from a lemonade stand.

Shiv: I agree. The money is obviously what funds a lot of this and gets people like Dominique your Chief Scientific Officer because they obviously have to have a living and you need people to do that. But there are so many other things I know that we can all do to reduce the friction. For our part at Osmosis, largely, what we're trying to do is motivate a lot of our current and future healthcare professionals to pay attention to these disorders and maybe dedicate their clinical careers to them because they could be that head of genetics you mentioned at Columbia, that person who is a lifeline for many patients and families like yourself. 

One of the reasons we're excited about joining Elsevier is that they bring all the research experience. We have over 2,500 journals at Elsevier and they have published research not only from researchers, but patients, patient perspectives. Tania and I have spoken about the need for a journal of rare disorders or being able to provide open access to research, like Elsevier has done on so many of their rare disease articles.  That actually is a long intro to a question I have for you which is, what more could Osmosis or Elsevier be doing -- or even the research/clinical community -- for KIF1A specifically, and also the rare disease community in general?  

Luke: Yeah, that's a hugely important question. I think Tania is somebody who's got a skill set to tap into when it comes to really driving policy.  I think that every bit of science needs to be promptly shared in an appropriate way. Intellectual property needs to exist to share things appropriately, not to monopolize things. Everyone has the right to learn about their disease, and everybody has the right to learn about therapeutics that are in development for their disease. I have this kind of personal policy that I never speak at a conference that doesn't allow patients or caregivers or advocates in for free. A lot of these conferences cost thousands of dollars, so free access is about creating citizen scientists and enabling families to take part in the process. Integrating that into the process is the only way we're gonna get there faster. 

CZI has this wonderful mantra that I love, and it’s become a mantra of ours too: science is better together. Well, it really is, and so I think that your point about having patients and caregivers co-author papers is really important. You have to have that convergence of science and experience. So many parents are scientifically savvy and can inform elements of the disease that don't show up in your traditional peer reviewed journals, right? 

But on the other hand, I think when people in the scientific community do come to a meeting or do come to an event or do come to a place where they're talking about rare disease, they need to do their homework. That homework is, yes, reading all of the major publications from every big journal that come from well-funded studies. But you know what? There are also blog posts, there are platforms, there are stories that patients and families have written. My friend, Mike Porath, started a platform called The Mighty and it's something that gives people an opportunity to write and share stories and those stories are just as important as the peer-reviewed journals. Your homework isn't just to read the latest peer-reviewed journal.

Shiv: Yeah, absolutely. It's a combination of those datasets, I think, that ultimately will help us better understand especially heterogeneous diseases, and then find those cures and therapies for them.

Luke: Also, it’s important to enable families to measure things at home in a way that's going to be accurate and helpful, right? Two years ago, we started collecting information in a very organized way on Susannah's seizures and her falls. Those are two endpoints that have now become very important in our endeavor for a therapeutic. We've been really lucky to have people like Tania, like Wendy Chung, like you who educate us and enable us to create the tools that are really needed so we can go to regulators and say, "Look, here's a very, not just validated, but standardized diary and collection of events that might be able to help move things forward." 

When the educators or people with really wonderful skill sets share their skill sets and educate families and patients, it's so critical. I can't tell you. I say this a lot, so forgive me for repeating myself but when Susannah was first diagnosed, I did -- as everyone does -- a huge dive into publications and trying to read things that were way above my head. If somebody had just told me that the word variant and mutation are the same thing, that would have saved me hours and hours and hours. I think that if you have a big scientific skill set or policy skill set, having that passion to share it with people who might not is something that we'll be forever thankful for. 

Shiv: That's a very helpful specific example. Something we strive to do at Osmosis is reduce jargon so that the same video we make on a rare disease is something that a patient will understand, a family member will understand, a researcher will get benefit from, a clinician -- so bringing everyone to the same sort of shared vocabulary while not losing the nuance or the actual science around it would be important.

Luke: Yeah. When I listen to your work, and when I see what you guys have done, it's right in the wheelhouse of what needs to happen. It's making the science colloquial.

Shiv: Thank you. Appreciate that.

Luke: Thank you.

Shiv:  I want to end by asking what other things do you want to share with our audience that we haven't gotten to yet? It could be about your work at Ovid, it could be about really anything that's on your mind that you want our audience to leave with.

Luke: When I think about the foundation,it's just a passion, and the thing that is really the litmus test is whether or not you can maintain things and whether or not things have a lasting ability. We're five years into our foundation, and we're going to learn a lot about ourselves if we can be ten years into our foundation, right? And similarly, in biotech, if somebody's got a preclinical program, if that preclinical program is around until it becomes a clinical program and a therapeutic is great. We have people in our community who have lost kids. Their children have died tragically -- and live on in science because they've donated their brain or spin -- and those parents are still critical members of our community and active members of our community because they have a lasting commitment. 

There's nothing more evident about a community that's going to be lasting than if you have those tragic circumstances, but people are still community leaders. I think that every stakeholder should do everything they can to enable the community to last and be relevant for however long, whether or not you have a therapeutic. I think that's huge. Anybody who can enable a community to last the test of time is a really valuable stakeholder to all of our communities. So, it's lasting, it's just showing up.

Shiv: That's awesome. I agree. That's really great advice to end on, and hopefully, something other patient organizations can emulate that KIF1A has done a great job with. So, Luke, thanks so much for taking the time to be with us today and for sharing your family's stories. It's really heartwarming, and we're hoping for the best outcome for her specifically, and then, obviously, your commitment to the overall community.

Luke: Thank you and thanks for giving me the opportunity to be here and for elevating our whole community. It means a lot to us. So, thank you.

Shiv: Absolutely and with that, thank you to our audience for listening to today's show. I'm Shiv Gaglani. Remember to do your part to raise the line and strengthen our collective healthcare system. We're all in this together. Take care.