The Journey of Susannah’s Personalized ASO

Luke Rosen:
Susanna's legacy is going to be one of a pioneer, as I keep saying she is going to be a pioneer as her brother. But I think what I hope for the future is that we have more standardized tools to measure disease and to measure efficacy. 

Mary Parker (00:43):
I'm Mary Parker and welcome to Sounds of Science. Today we're honored to speak with Luke Rosen about his incredible daughter, Susanna, and the mission behind KIF1A.org, an organization dedicated to advancing research and hope for those affected by KIF1A associated neurological disorder, also known as KAND. From groundbreaking treatments like antisense therapies to the power of collaboration, we'll explore how Susanna's story is inspiring progress in rare disease research. Welcome Luke.

Luke (01:18):
Thank you. It's such a pleasure to be here. I appreciate it. Thanks for having me.

Mary (01:53):
Tell us about yourself and your family.

Luke (01:58):
We live in New York City. I'm currently traveling, but I have just a remarkable family. I'm so lucky to have an incredible wife named Sally who really is our anchor. And when people say I'm the founder of the foundation, that's kind of incorrect. I'm really the co-founder because Sally has so much to do with this and my two children are just incredible. I have a 13-year-old Nat. He's a wonderful young man who is 13 going on 60 because of all the things you had to go through really. He's just an incredible older brother to Susanna. When Susanna was born, she was diagnosed with KIF1A-associated neurological disorder, and she is currently on year two of treatment with that ASO or antisense oligonucleotide and she's just an incredible kid.

Mary (03:18):
So what makes Susanna, your KIF1A superhero?

Luke (03:23):
Susanna is a pioneer. When we were starting this whole process, working with our doctors and researchers and other collaborators, and I'll speak to, and Lauren, which along with Charles River and other wonderful organizations have really made this possible. We all kind of tag-teamed it. We said, okay, we have to develop this clinical trial together. We have to, and no one’s done it before and let's try it. And for us, with KAND, there's no other treatment. Everything is completely symptomatic. And so when we understood that there was an opportunity to actually address the snip of RNA that is causing all of these challenges, we said, yes, of course, but we were the first. And that was hard. But since then there have been, there's been another younger child who's been able to have this intervention that Susanna had first. So we're still swinging through the waters as being the first, but I say that is what makes Susanna really a superhero, is that she's a pioneer.

Mary (04:53):
And we're going to get into the details of the condition and how it's affecting you. But first I want to talk about KIF1A.org. Obviously is very important to you, and we're going to put that link in our show notes for anyone who's interested in checking it out. Can you tell us how the organization got started?

Luke (05:11):
So when Susanna was diagnosed, she was one of seven that we could find in literature really. And when we went to the child neurologist, I went without the family there. When the geneticist had told us what this one of our doctors had told us what this disease was and the implications of it and had printed out this said, I don't know much about this, but here's an article, a publication. And that publication had a horrific scary title called Mutations in KIF1A cause Brain Atrophy and Death. And so that's certainly what we weren't expecting. And I got home and went into the kitchen where Sally was standing and I knew I had to tell her what I had just found out about this disease. And I remember there was one fleeting moment where she had her back to me and I thought, okay, I could give her another two minutes or however many minutes of not knowing this, but I didn't. And I told her and there was a lot of crying in our kitchen. And then we decided that we would activate and got in touch with another incredible physician who ended up being our real champion. Her name is Wendy Chung. And I had been googling everything of course, like most do, and trying to find every single doctor, investigator, researcher who had anything to do with KIF1A. And of course we lived in Harlem and it was around the corner at Columbia after all.

Mary (07:14):
That's lucky.

Luke (07:15):
That is lucky. I mean, our kids were born there. If I needed stitches from a bike ride, I would go there. It was just, Columbia is really a home for us and the people there are just really remarkable. And we started put a website up and uploaded all of the documents that we could find in PDF, and that's where we broke the law. And there weren't many. There was one clinical paper and then the rest were all very into the weeds research papers that I, at the time certainly had no, excuse me, certainly had no skillset or knowledge to interpret, but I thought that would be a good idea is to have all the literature in one place. And so we just bought the domain, KIF1A.org and uploaded all of the documents, all of the publications as PDFs, so anyone could access them.

Luke (08:16):
And at the very bottom of the page, we put, call us, here's my phone number. And we certainly didn't set out to start what we have now, but all of a sudden people began to reach out and they had received this diagnosis. So we went from seven to 10 to 35 to 45 and so on, kept growing exponentially. And then where I really decided, or we really decided that, okay, this needs to be a movement, this needs to be a way to find therapy and a way to find other families was a father called me and he said, my daughter was just diagnosed with this disease and they were an under-resourced family. And I said, well, did you read the literature? And he said, I couldn't afford the 30 bucks on PubMed. And I thought, my God, every person deserves to know about their disease and read this.

Luke (09:14):
And so I shared that website with him and he was able to learn just as much as we were. And so I guess our mission became to find more families and to make sure that everybody was empowered to learn about the disease and do something about it. I always say that every single person has a skillset. Everybody has a skillset that can make an organization or a group or family better. And I'll tell you, by empowering and by opening up a door for somebody to use that skillset to help a community, especially a rare disease community, was remarkable.

Luke (10:04):
We had a conference in 2019 was our first family conference or really our second one. The first one was a month after diagnosis, and we had seven to 10 people in a little room in Columbia. But in 2019, we had a big conference and we couldn't afford much. And the biggest cost was going to be a shuttle bus to get families from the hotel to the venue at Columbia. And we had a family whose mother was a bus driver in Kansas and she drove the bus for free. And so all of a sudden everybody's using different skill sets to make the community stronger and better. So yes, in short, that was a long answer too. We set out to find more people and to raise money to support a preclinical program.

Mary (10:59):
Well, we'll definitely be getting into the importance of collaboration, which that obviously falls into in a minute. But first I'd love to hear more information about KAND. So what is KIF1A-associated neurological disorder or KAND?

Luke (11:16):
KIF1A-associated neurological disorder or KAND, I'll call it KAND from now, is a mutation in the KIF1A gene and it's novel. And in our case, it's not a hereditary condition, it was a spontaneous mutation for Suzanne. So it just happened. And we've since learned we have their 80 somewhat different mutations on the gene. And each, no one person is exactly the same of course, but Susanna's case she was or is the more severe on the spectrum. And she has uncontrollable real epilepsy. She's having hundreds of seizures a day. She has spastic paraplegia, which makes it very challenging for her to move her body to walk and horrible neuropathic pain, which sends pain down her legs. And K, it is a degenerative condition because it really is nerves dying and trophic nature of the disease, including cerebellar atrophy, which is a difficult part of everything. There's a myriad challenges people have, but those are the pillars.

Mary (12:43):
And when did her symptoms start? How has it progressed?

Luke (12:47):
Yeah, like I said, my wife is so incredible, and we knew being your second, Suzanne was our second child, as I said, and with Nat being our first child a couple of years before, if you got a bee sting, we would rush 'em to the ER. But it's like the second kid is, they'll get there on their own. They're on their own. Don't worry about it. But we did know that something was significantly wrong with our health. And when we realized that it was time to really take action was Sally was giving Susanna a bath, and we always, with the kids, we would say, kick, kick, kick, kick, kick your feet. And one day we realized that Susanna couldn't kick or move her feet, and that prompted our action to take her to a doctor. And there were a few other moments of crisis that really cemented that we knew something was different about Susanna.

Mary (13:52):
I imagine that must have been an incredibly scary time for your family. Did that drive the work you're doing at KIF1A?

Luke (14:02):
It did, of course. Yeah. It is very isolating. And when you think, oh my gosh, this is so, so difficult. I was walking Susanna up Amsterdam Avenue and her stroller, and all of a sudden her legs shot out like planks, and she started crying and horrifically. And that was really because of her neuropathic pain. We know now, but at the time I didn't know and I was terrified. So I scooped her up and took her to the emergency room. And all of those sort of that perfect storm or imperfect storm of frightening moments really said, okay, we can't be the only ones like this. We need to find other people and find our tribe. Really. We went out and we did that.

What role does genetic testing play in a KAND diagnosis and is a misdiagnosis common?

Luke (15:17):
A misdiagnosis of can was very common now, thankfully it has changed. And how that's changed is through genetic testing. There's been sort of three moments of progress or three moments of real innovation that has happened. And I think it was driven by, I know it was driven in many ways by other rare disease organizations like us. If you look at the numbers, statistically rare diseases aren't very rare, right there. One in 10 people have a rare disease. So when I'm sitting at a large room doing whatever I'm doing, in my mind, one in 10 people are touched by a rare disease in some way. But yeah, and again, with the advice of Dr. Wendy Chung went to every single genetic testing company, and that took a while. I would sit in waiting rooms and stock people. I'm kind of good at that. But what we did, you might not know that if a child walks into a doctor, and it's not a very savvy physician who is proactive about genetic testing because of cost, because of coverage, because of whatever reason, they send out a single panel gene test, which is my kid has a seizure disorder.

Luke (16:50):
So what the doctor will often do is send their blood off for gene testing for seizures. So there you're on a seizure panel and you get sent for seizures if you come into a doctor with vision problems or the physician will send your blood off to a vision panel for genetic testing, similarly with different challenges. And so we went to found the similarities that our kids had, and we knew that, like I said, the pillars were movement disorder, vision loss. Our kids have optic nerve atrophy. I think I forgot to mention that, seizures and a few other things. And so we went to those companies was can we please get KIF1A on those panels? And so when a doctor would send something out to a genetic testing lab for vision problems, one of the genes that would come up is KIF1A, allowing the family to get a diagnosis.

Luke (18:03):
Whereas before that, the gene wasn't on those single gene panels. And so that was a good thing because we said to the genetic labs, is there any chance that you could put our website down as a resource for a person who gets a diagnosis of KIF1A, because we can support them, but we also need them to be participating in research to understand the disease more. And so our organization quickly became a very scientific and supportive advocacy group. And then things started changing when whole genome or exome sequencing became more accessible to people. And I'll speed ahead to just a few years ago, two years ago when Medicaid started covering whole exome or genome sequencing in, I think right now we have 10 states, but one of the first states where Medicaid covered those extensive genetic testing was Michigan. And within a month we had 25 families from Michigan. So we knew right away that this disease was far more prevalent than is appreciated at the time. And we're finding out that that's the case now too.

Mary (00:10):
So I understand that on your website you put out a call for other families who might have KAND and that initially a lot of people with KAND were misdiagnosed with cerebral palsy. So can you tell me a little bit about how many families have reached out to you since then?

Luke (00:32):
It's an incredible question, especially when you open the can of cerebral palsy and genetic etiologies of that disease. So right now, a lot of people have big registries and platforms that they, ours is still a Google doc. We collect very specific data, including mutation, and we de-identify it. I think there's a big difference between something being de-identified and recontact able, right? And so if somebody needs to contact a family that has this mutation or this challenge, we're very able, we can easily connect people. But right now we've grown from Susanna being one of seven to about 750 families globally. And cerebral palsy is, and this is a really important topic that's very relevant and also people are really, it's a hot topic right now, is that cerebral palsy by definition is caused usually by head injury or by something that happens at birth. It's not a genetic disease.

Luke (01:48):
It's a bucket that before we were able to understand these diseases that have acronyms that no one can understand, including me, if a doctor couldn't figure it out, they'd put them in the bucket of CP. Right? So almost everyone, including Susanna at some point, has had a diagnosis of cerebral palsy. What we know now and what people are working on, like the Weinberg Cerebral Palsy Center at Columbia has become a real Susanna's neurologist, leads that, and has become a real precision, it's gone from a CP clinic to really a precision medicine clinic because we're starting to understand that everybody who has, not everybody, but I would say a huge portion of the population who have cerebral palsy, there's a genetic reason for that bucket diagnosis of cp. And that's another really important way and reason for community to galvanize is it's not just K1A.

Luke (02:51):
It's not just us who are building a community because of a misdiagnosis of cerebral palsy. It's every gene, every genetic disease, certainly benefiting from people going, I would love to go somehow find everybody with cerebral palsy and sequence them. I guarantee you that we would have so many, there would be no such thing as rare disease if we sequenced everybody with cerebral palsy and found that genetic Cause. A problem that exists therein though is it gets into services and how people get their physical therapy, their occupational therapy, their speech therapy, their vision therapy, they're moving is cerebral palsy has an ICD 10 code, right? It's coded to be billed. It's coded to get the treatments. And a lot of these genes don't have those codes that hospitals work with. So some people when they get that real genetic diagnosis, but they've been living for so long with a diagnosis of cerebral palsy, say, I don't want it. I have cerebral palsy and I'm getting all of the services that I need, so don't give me a diagnosis that doesn't allow for services, right? So it is very a tricky situation, but that's another resource that we point people in the direction of is the Weinberg Cerebral Palsy Group at Columbia. They're very good at providing those genetic tests.

Mary (19:28):
Yeah, that'll happen when genome sequencing becomes more prevalent. You'll see common factors that wouldn't be accessible with any other treatment or any other diagnostic criteria. So speaking of treatment, what treatment options are available for patients with KAND?

Luke (19:58):
Yeah. Treatments that are available for KAND up until two years ago were purely symptomatic. They were small molecules that we could use to attempt to control seizures. There are so many seizure meds out there, which by the way, and this is a side note, I really do believe there should be, when people are talking about getting lots of genes into a newborn screening panel, people say, well, we can't do it because there are no treatments. Well, so many of these neurological diseases have seizures as a phenotype. So hey, you can rationalize, look, there is treatment, there is seizure treatment, and so they might not work. But that's one sort of shot on goal or one string of spaghetti against the wall.

Luke (21:06):
The tricky part is the optic nerve atrophy and the atrophic nature of the disease is one of those parts that's so hard because there aren't small molecules that you can use for degenerating and deteriorating brain cells, or there was only one or two therapies on the market that were available for neuropathic pain. And really none of them worked for us and for other rare disease communities. And so the treatments were purely symptomatic would address them individually until, and our doctor champion Wendy Chung, I'll keep mentioning her name because she's just part of our extended family and really did drive this from a research and a clinical perspective, but early on she said, kind of try to stick next to the Huntington's community

Luke (22:22):
Because it's going to be a similar mechanism of action that addresses this disease and there's some similarities. And so we did. And the treatment that the Huntington's community was at the time, going through a clinical trial, but also really exploring was an antisense approach, and really looking at a little tiny snip of RNA that's causing the problem and addressing it, the difference being, and with other diseases that target that an ASO will target, there are fewer mutations or fewer, and we now know it's not mutation specific, it's RNA specific. And so there, they're just different. There too many, it's too heterogeneous to really pin down. That's why it was such a difficult task for all of the developers and collaborators and physicians and researchers to approach and to really execute. And the Huntington's community was pursuing an ASO, so we did all we could to bang down the door of every company and lab that we're working on antisense approaches. And finally we did find somebody who opened the door for us.

Mary (23:53):
So you mentioned Huntington's. Are there any other ultra rare diseases that you've heard of that can be treated with antisense oligonucleotides?

Luke (24:01):
Yes, there are. What was hard, a hard, no pun intended pill to swallow, was that the antisense technology has been around since the eighties. And we saw during covid, which everyone, when you focus resources and focus attention, you can attain or develop what we had been trying to do for years. And that's an mRNA approach to therapeutics and diagnostics. And so I thought, oh my gosh, this has been around for so long and it's so hard to do. But yes, there are other diseases, other monogenetic and conditions that can be addressed through an antisense oligonucleotide. And I know folks like En Loam and Stan Crook and others are really focusing on making ASOs widely available instead of going through a, well, I mean, they do go through rigorous process, but focusing on one clinical trial for one disease. Right? We're looking at it more gene agnostic and mechanism specific. So we have diseases like SCN2A or other rare epilepsies. Of course, Huntington's is still looking into ASOs and even early onset ALS. So there are several other diseases that can benefit from an ASO.

Mary (25:38):
It sounds like ASOs can be tested in terms of their mechanism of delivery, but then once that's approved, it can be used on almost any gene without the need for a lot of extra safety testing because that's already been done based on the method of delivery.

Luke (26:01):
Yes. I think one thing to add to that that's incredibly important is the degenerative urgent nature of disease is something that our partners at the FDA really are wonderful and appreciating and understanding. So there was a pre IND meeting, which I'm sure your listeners and everybody knows what an IND is, but I'll say it. It's the very, very long process of putting together a package to submit to the FDA for rationalization of use. And in the pre IND meeting, it was explained to the regulators that this disease is unfortunately fatal, and the kids who have this disease have nothing else. And the FDA very easily could have said, well, for safety purposes, we need more data. Instead, they said, the science and the safety that the collaborators and the developers of this was so strong, it's got such a strong safety profile that we can do this with two weeks toxicology. So that was remarkable because we were all crossing our fingers and waiting, and FDA said, this is such a strong molecule, is such a strong high safety profile or strong safety profile that we can move forward rapidly.

Mary (27:51):
I mean, that brings us nicely into our next section where we were talking about collaboration, the importance of collaboration from everyone from your FDA partners to bus drivers. Can you tell us about the partnership between KAND and n-Lorem? What inspired this collaboration?

Luke (28:08):
Yeah, that's great. We can talk about specific collaboration so I don't throw it all together. There were really army that was behind this. So specifically talking about n-Lorem is a team of incredible people who care passionately and relentlessly about every one of the patients who apply to become part of it. And what it is is It's a nonprofit that has a very ethical way of selecting patients who apply. Your physician has to apply, and you have to have a condition that I believe affects under 30 people. And that number, while KIF1A, we found hundreds of people. Now there are still only four or five kids with each different and heterogeneous diseases. You get the snip of RNA that could be targeted with an,

Luke (29:19):
That's a hard thing to understand, but for the disease population. But it is one of those points of application. And so our physician applies and the applications are blinded, so there's no name attached to it or anything. And they have a process of different phases where there are clinicians and researchers and people with lots more alphabet suit behind their name than I have who decide A, whether or not this condition and this application is truly ASO-amenable, and B, if this is a process that can happen in time to really benefit the patient. And when our doctor, Wendy Chung, our champion had applied for Susanna, she was one of the first who had an application in, and of course as you know, she was accepted. And it was at the time a two year process. But that's shortened significantly. And that goes into one of, when I call Susanna a superhero, it is that pioneering toughness, and I have a few favorite words.

Luke (30:48):
And impact is one community is the other and grit is the other. And Susanna has a lot of grit and she's very tough. And so she was selected and n-Lorem partnered with an organization that came and drew her blood and sent it off and they started working. And that's a drastic understatement when I say they started working. They with other people, CROs like Charles River and other people who are working as passionately as the team behind all of this set out to make thousands of ASOS until they found and optimized the one that would hopefully help Susanna. And so they made an ASO that targeted that little snip of RNA that we were talking about. And that was the process of making Susanna's ASO, which thankfully now hopefully could help other kids too.

Mary (31:58):
Can you share some program milestones or successes that you've had so far from this partnership?

Luke (32:04):
Yes. The partnership, it really is like a new family that has started. Of course, people are checking in every single day. Thankfully, there haven't been any safety issues or adverse events that are related to the drug. I mean, Susanna still has challenges, and this is certainly not a cure. That's something we should be very upfront about. And as is not a cure, it's a bigger molecule that has genetic based qualities about it, but it's not a cure. It's designed really to hold off progression and curb the severity of disease, which is game changing. And so the first milestone was getting the drug, and it's a very difficult process. It's an intrathecal lumbar injection. So our little girl was getting lumbar punctures into her spine. She gets the treatment. And a lot of people say that's one of those factors that you have to measure as risk benefit is do you want to be anesthetized and have that lumbar puncture every few months? And for us, of course, what's the other option?

Luke (33:31):
And that was a big milestone. And we have the actual empty vial of the first treatment. And when she woke up, and that was pretty incredible, just her being there. And then cut to a few months later, she stood for the first time, and in several years she had lost the ability to stand and to walk, and she stood up and she was able to walk. That was a huge milestone. And what has been most remarkable about this intervention for Susanna is her seizures. The seizure reduction has certainly been incredible, but her cognition and her ability to engage and to have energy and endurance, she used to not be able to make it through three hours of school because something would happen and we'd have to come pick her up. Now she can make it through an entire day. It's not a standardized clinical endpoint, but she can make it through an entire baseball game, which is a long thing. And so I kind of looked at it like innings, right? She can now make it through nine innings of baseball, and she has an attention and she can really, there was so much inside of Susanna that now can come out and she has an ability to communicate with people in a way that she didn't before. And that's just, she has an independence that every kid really deserves to have.

Mary (35:15):
That's remarkable. Witnessing something like that firsthand, I wouldn't be surprised at all if Nat takes up an interest in science and getting into that sort of field himself.

Luke (35:26):
Yeah, I mean, Nat has been through so much of this. I mean, he is quite literally saved Susanna's life before in a few different circumstances, especially revolving around epilepsy and seizures. One of us wanted to, Sally or I sleep in the same bed as Susanna, hoping she won't have a seizure at night. And there was one moment where that wasn't the case. And of course that's when Susanna had a seizure and that was next to her and he knew what to do, and now he's 13, so he's gone from, he's had quite the evolution of being a brother and understanding this. And at first we really wanted to protect him from everything that was going on. I never wanted any of our kids to know that we're degenerative, degenerative nature of disease. I never wanted our kids to learn that word degenerative. But he started, he's able to go on the computer and read and learn.

Luke (36:30):
So we did have, he'll ask questions like, will Susanna ever drive? And the answer is no. She's not going to ever drive. She still has severe cognitive issues. They're getting better, but there are little things that she won't be able to do. And he's starting to really understand that. So he's incredible, and I've said this before, but it is, the part that gets me very emotional is when Dr. Chung was explaining the implications of this disease to us in this small room at seven 30 in the morning, Sally and I were there. I said, she was telling us all these that our kid was going to be in a wheelchair, was probably going to have seizures, and we weren't too long. We weren't too sure what her prognosis would be in terms of lifespan and blind. All of these horrible things we're hearing. And the only thing that I was thinking of at one point was, well, how am I going to tell Nat? I'm going to tell her older brother about this? She looked right into my eyes and said, he is going to grow up and be a remarkable young man. That's true. He is a remarkable young man who is very teaming with empathy, especially for his sister.

Mary (38:06):
That's amazing. And speaking of saving lives, I understand that you as a fireman might be in a unique position to help rare families dealing with the California wildfires.

Luke (38:18):
Yes. Thanks for bringing that up. We are, and we've started another foundation that's somewhat separate from KIF1A.org. It is separate as an organization, of course, it's called Rescue seven Firefighters for Patients. And what we do is really help families. And as a firefighter being on, I'm a search and rescue task force, New York State, one of, and we had to really, really, really, really fight for this on the hill was to have a group of search and rescue firefighters really going to, in natural disasters and other moments of crisis, to go and seek out and help special needs kids, not needs kids, but everybody with special needs and connect them with their caregivers who are often displaced, especially out here in the fires right now. This started when we went down to Florida to work on those horrible hurricanes. And I had a nightmare that was very recurring that if Susanna was on someone like Susanna, but my night went with Susanna, was on a raft in the middle of the road floating down the street.

Luke (39:39):
If one of us said, Hey, are you okay? She would, being Susanna, she would just smile and wave. And those people who were out there trying to save her life would think she would be okay and she would not be okay. And so we try to get funding to be able to help people, especially with cognitive issues, Alzheimer's disease and things like that. And we've already, in California at these wildfires, one of the things we do is identify, go to the different safe areas and identify people who rely on the caregiver and who have been separated from that person. And the relief when somebody finds a caregiver in the middle of what could be an apocalyptic situation.

Luke (40:35):
Is something that I can relate to. And so as well as doing search and rescue will help everybody, of course, that we find it's our duty and our mission, but we have an extra mission, and that is to make sure that no kid is left behind or no person is left behind. Especially those people who have challenges similar to Susanna's, and that transcends KIF1A. That is Alzheimer's disease. That's when we all become one community.

Luke (41:16):
It happens through challenges in devastation, diagnosing, being diagnosed with a rare disease you find. So I have learned so much from other rare disease organizations and other rare disease families and taking pages out of their books, and we all work together, we all work together, and we all learn from each other. And that ethos of community can become part of, like I said, every skillset.

Mary (41:56):
I'm sure there's protocols for evacuating hospitals and nursing homes, schools, things like that. But as you mentioned, a lot of these special needs kids are probably cared for at home. So it'd be a private residence. They may not be in an official registry for people that need to be checked on. So it's good to keep those in mind and to have people like you coming up with ways to help them and reconnect them with the people that need to give them care.

Luke (42:28):
Yes, that's a great way of putting it, but I would say lots more people than me. It really takes a team. But it's terrifying for somebody who I imagine is terrifying for somebody who has Alzheimer's disease, let's say, and is rescued, but is rescued and is in an atmosphere that is completely chaotic, where people are very injured. It's a very chaotic couple of days when they're in a safe shelter that people have worked so hard to create. But there are people who are completely alone and are confused. And sometimes I think that can be just as dangerous as being under a pile of rubble.

Mary (43:24):
Absolutely. Well, switching gears a bit. In your opinion, what does the future hold for rare disease drug discovery and development?

Luke (43:33):
The future of rare disease drug discovery and development is to join forces and to recognize that one therapeutic isn't going to just work for one person. There's a way to scale it. And so I think that if we, again, start looking more disease agnostic and mechanism specific, we're going to be able to discover and actually deliver treatment to multiple different people. So I think it's really, again, that word that means so much to me, community becomes just critical because there are going to be different rare diseases and different diseases that by coming together with every stakeholder, from policymakers to clinicians, to researchers, to CROs, to everybody who's working on this, to come together and have an aha moment where this therapeutic is going to work for multiple conditions. So to answer your question, the future is about community and collaboration, and I think that we're getting there.

Mary (44:53):
And what advice would you have for families affected by KAND and other ultra rare disorders?

Luke (45:00):
To activate, but you can't activate until you find your community. So find your community, lean on your community, grieve with your community, and then activate to participate in moving the needle forward with research and with eventually a therapeutic that is going to help your family. So I think it really is about leaning on each other and being compassionate and understanding that we're all in this together.

Mary (45:38):
What does the year ahead look like for Susanna, and what do you hope her legacy will be?

Luke (45:46):
Susanna's legacy is going to be one of a pioneer, as I keep saying she is going to be a pioneer as her brother. But I think what I hope for the future is that we have more standardized tools to measure, to measure disease and to measure efficacy. And I'll tell you this, is that the first clinical trial for Susanna, we were all kind of like, all right, let's try this. We know this is a hard endpoint. People need to see seizure reduction, so that's going to be an endpoint. And what we didn't expect or realize is that Susanna had very big tremors eating or drying or anything. She was so tremor and we weren't measuring, that wasn't an end point. But the most significant physical thing that has happened, Susanna, is that her tremor has gone away. And people wouldn't think how much independence and freedom that gives our family is able to sit and have a meal with, I would one, always being right next to Susanna thinking that she's going to either choke or that she's not going to be able to eat because we're all able to sit there and there's an element of calm to it, but it's also a Parkinson's disease.

Luke (47:13):
I mean, it's a horrible condition that really affects people. And it is that movement disorder and that tremor and that shaking. And we had to re-look at the clinical trial, and thankfully, Friedrich's ataxia, another rare disease had just had a tremor scale approved to use. So we were able to integrate that into Susanna's trial. So to answer your question and to get back to community, I think that what I see in the next year is people learning from Susanna's trial design and designing a trial that actually results and yields data that is unquestionably strong, right? Because absolutely, we're measuring the right pieces of disease, and we have these tools that are standardized to measure them. And right now we don't. And the FDA is really ripe for it and waiting. So my goal for the next year is to make these ASO clinical trials a little smoother, and hopefully people are doing that in learning from our pioneer,

Mary (49:09):
And what can our listeners do to help you achieve your goals?

Luke (49:14):
This is a great question, and I say it's a dangerous thing to ask me, what can I do to help? Because there's always

Mary (49:22):
Something,

Luke (49:23):
Right? And so a lot of it is in kind donation, like things that Charles River does, things that other CROs do, things that Stan Crook and n-Lorem do. I mean, they have this do this all for free for life. And we never would be able to have this therapeutic if people weren't applying their scientific skillsets to be so passionate about patients and people and families like ours. So I would say yes, everybody needs money, so things can't happen without resources. If that's an easy route, yes, support research that's happening. But I think more importantly, people have to realize that that research exists and we just need to focus it on what people often and in the past would say, too rare. That's too rare. I'm not going to invest in developing a therapeutic for that. Well, it's not too rare anymore. And so I think that investing effort to develop therapeutics for rare diseases is what could impact the entire rare disease community most.

Mary (50:39):
Well, Luke, thank you so much for being part of Sounds of Science. We really appreciate you coming on and telling you and your family's story.

Luke (50:47):
Oh, this has been a great honor and a pleasure, and thank you for all of what you do and for having me here. Thank you.

Mary (51:21):
Luke Rosen is founder of KIF1A.org. Stay tuned for the next episode of Sounds of Science. Until then, you can subscribe to Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Thanks for listening.