Stephanie Sirota: There's a little girl named Elly whose parents didn't give up in the face of a rare diagnosis, a ticking clock, and a potential path to a cure. In 2025, Elly received gene therapy treatment for her condition, one of the fastest of its kind ever deployed. And today, we have the privilege of hearing her story.
Welcome to the RTW Podcast. I'm today's host, Stephanie Sirota, Partner and Chief Business Officer leading the Strategic Partnerships Team at RTW Investments. I'm also on the board of the RTW Foundation, the philanthropic arm of RTW, powering rare disease research, medical innovation, and local community collaborations.
In 2024, we partnered with Elly's Team, a foundation established with the singular goal of translating medical research to treatment in record time. Today, we welcome Michelle Krueger, Managing Director at Alvarez & Marsal Transaction Advisory Group, the Co-Founder of Elly's Team, and Elly's mother.
Michelle, thank you so much for joining us today.
Michelle Krueger: I'm so honored and humbled to be here.
Elly’s Diagnosis
Stephanie Sirota: Why don't you just start telling me about your family?
Michelle Krueger: I have a six-year-old, a four-year-old, and Elly, our sweet baby that we're here to talk about today.
Stephanie Sirota: What was her early infancy like? And were there signs that something was wrong?
Michelle Krueger: Pregnancy was completely normal. Birth was normal. She passed all newborn screenings. She ate well. She slept well. Around five months, I remember looking at her and noticing kind of a flicker in her eyes. And it was so quick, you would miss it. She also wasn't developing quite as I would expect with the other kids.
Stephanie Sirota: Did you see a doctor?
Michelle Krueger: The Wednesday before Thanksgiving, I couldn't dismiss it anymore. Our pediatrician, I texted her and she was like, “Just bring her in today. I'll fit her in.”
She looked at her. She saw the flicker. She said, “I hate to say this, but I think you need to go to the emergency room.”
We live on the Upper West Side. The parade was getting set up. I mean, all the tourists were in town. The emergency room in New York City is never a fun place. But they were incredible that day. We did every test imaginable on Elly. We were there for hours. We got an MRI. And then around 2:00 or 3:00 in the morning they said, “We don't know.”
Fast forward to Thanksgiving Day. We got home very late. Woke up the next day. Very somber mood. Dan, my husband, and I kind of put on a happy face for our older kids. We went outside and watched the parade, which goes right by our apartment. And a couple hours later, we got the call.
That right there was probably the first miracle that happened for us. Dr. Zachary Grinspan, one of the best neurologists in the world, was on call on Thanksgiving Day.
Stephanie Sirota: That's pretty lucky. What went through your mind?
Michelle Krueger: You're paralyzed, and you're numb, and you know something's wrong, but you don't know what. When Zach called us, he quickly flipped it to a FaceTime, and she did the eye flicker. And he said, “I don't want to scare you guys, but I think it's seizures. And the only way to know for sure is to come back to the hospital and do an EEG.”
And within 20 minutes of having her hooked up to the EEG, Dr. Grinspan said, “She's having infantile spasms,” which is a type of pediatric epilepsy. When you have infantile spasms, there's three main reasons. It could either just be truly random and medication solves it, or it's a genetic disease, or there's a structural issue, like a tumor.
The MRI mostly ruled out the structural side of things. We passed all the genetic testing. But Zach sent our results to the New York Genome Center as part of a clinical protocol.
We waited months. I remember during that time—it sounds crazy—but I was praying that she had a tumor. I was praying that she had cancer. When you're sitting here and you're thinking, “It's either a genetic disease, an ultra, ultra rare one because we've already passed everything else, or it's cancer,” I was choosing cancer as a mom because I knew it was well-funded and well-understood. So, it sounds absolutely crazy to be thinking that way, but I just knew in my gut that a genetic disease was going to be difficult.
Stephanie Sirota: So what about the day that you received Elly's diagnosis? It was months from that point, so now that takes us into February 2024.
Michelle Krueger: The New York Genome Center emailed and said, “We just released the results to your clinician.” And Zach said, “We have an answer. It's not good.”
Finding a treatment with RTW Foundation
Stephanie Sirota: I can only imagine that receiving this diagnosis and knowing that there are no existing treatments available could be paralyzing for some. But it wasn't. It was motivating for you. Can you tell us what steps you and Dan took after learning about Elly's condition?
Michelle Krueger: For me, action was easier. That first month or two, you can let the devastation swallow you whole, or you can decide to fight. We ultimately both decided to fight.
Dr. Grinspan said, “It's really, really rare. I can only find 40 kids in the publications. There's two main papers. But what I'm reading isn't good. It seems like it's progressive, maybe neurodegenerative. There's no treatments. There's no cures. But there's this one scientist, Dr. Kathrin Meyer out of Nationwide. She wrote this paper. I quickly made some calls to all of my friends and colleagues, and they say, ‘She's the real deal. And she knows your disease.’”
We experienced so many mini miracles to get to where we were on April 3rd. And having Zach be on call, and then having Dr. Kathrin Meyer already know our disease, those two people were the biggest champions and advocates for what we did.
Stephanie Sirota: Let me just set the stage and then share some context for our listeners.
Before Elly was even born in 2022, RTW Foundation received a grant proposal from Kathrin Meyer, who was then a researcher at Nationwide Children's Hospital in Columbus, seeking a grant for the genetic disorder IRF2BPL, related diseases, and an AAV gene therapy to correct them.
Now, Joe Katakowski, Director of Research, thought, “Okay, there's a 99% chance this does not work.” He said you wouldn't want to apply a gene therapy because there's a dominant negative gain of function.
What this means is that the mutant gene out-competes the good gene. And even if you put more of the good gene in, the mutant gene will fight hard to win. IRF2BPL, that gene is a transcription factor. Transcription factor genes—they turn genes on and off, possibly hundreds. So, the RTW team was pretty much ready to just reject this grant. But Kathrin Meyer was able to show some evidence that the gene therapy could actually get the correct copy of the gene into the cell nucleus.
This was done in a Petri dish, not in animals, and certainly not in humans yet. On October 10th, 2023, the board of the foundation, which I am a member of, voted unanimously in favor to approve this grant.
And that was five months before Elly's diagnosis. How is that for a miracle?
RTW was the right place, perhaps the only place, to really quarterback all of the help that you needed for your daughter. So how did you first get connected to the RTW Foundation?
Michelle Krueger: We’re consultants. We know the importance of networking. So, we decided to create a little resume for Elly. We put her little picture in the corner and her disease and her symptoms. And we said, “Can anyone help?”
My very good friend sent it to her boss, who happened to be very good friends with Rod. And so, within 20 minutes, this resume got to Rod. And he replied to me and said, “We know this disease. I'm connecting you to Joe.”
And he taught us everything we had to know. The RTW Foundation from that point forward were really with us every step of the way.
Stephanie Sirota: What does the partnership with RTW Foundation look like to you?
Michelle Krueger: RTW Foundation has been a critical force in our ability to get this done. Joe Katakowski joined our board, and RTW Foundation partnered with us not only with funding to do our toxicity study, but they also offered the scientific advisory, where Joe was kind of our right-hand person.
He joined almost every call with me. He dissected the science with me. He helped us evaluate how to make the right decisions, and how to move forward. So, when we were talking to the ASO developers, who might as well have been speaking a different language to me, Joe was there and could chime in with the questions we needed to ask.
And he helped me and Dan navigate through this industry that we didn't know anything about before. He did it with a smile, and with hope and with love. I knew that behind him was the entire Foundation as well, and RTW Investments. And just knowing that I had that family and that we had that support, it meant so much.
Stephanie Sirota: There was another funny connection because Dr. Grinspan was an investigator in a very widespread pediatric COVID study. And we had donated to that.
Michelle Krueger: It's a small world when you start to really get into this. The RTW Foundation has been a critical force in enabling us to do what we've done, and I think the fact that RTW Investments invests into companies to drive science, and then the foundation arm takes that science and brings it to those that would otherwise not receive it, it's just this beautiful partnership that you guys have figured out. I can't express enough how grateful we are for the foundation's support.
Elly’s journey: from research to treatment
Stephanie Sirota: What were some of the biggest hurdles in your journey?
Michelle Krueger: The biggest hurdle was taking all of the information and all the different pathways, and then deciding, “What are we going to do?” Very little's known, right? There's preliminary research indicating there's this dominant negative aspect. But we also believe there's a loss of function because the protein isn't where it needs to be.
We knew at this point that Elly's disease phenotype was very serious.
She wasn't responding to any medications. Her seizures were not under control. She wasn't developing. We had to move quickly.
We knew we were going to start a foundation. Then Dan said, “I think it should be Elly's Team, because look at the team that we've already brought together.”
Stephanie Sirota: Because it is Elly's team.
Michelle Krueger: Yeah. And so, you know, we started the foundation.
Stephanie Sirota: What led you to ultimately the gene therapy?
Michelle Krueger: We dual-pathed it. In those early months, I got connected to another mother. And her son has a very ultra rare disease, a different disease. She gave me, like, a three-hour tutorial on, “You need to know the mechanism. And there's four approaches: ASOs, gene therapy, drug repurposing, and gene editing.” We pursued them all at the same time.
Stephanie Sirota: You became a drug developer.
Michelle Krueger: Yes.
Stephanie Sirota: And it must be incredibly hard knowing that what you're doing was not really a therapeutic candidate for a company, because there may be 40 patients characterized with this disease worldwide.
Michelle Krueger: At first, there were 40 kids documented. We now know that there's probably about 150 kids with it. You do the math, and you say, “This is never going to be a commercial product.” But it doesn't mean we shouldn't try for Elly and for all of the other kids.
Stephanie Sirota: That's the reason that RTW Foundation exists, to help fund and advance science that may not be commercially viable for a larger organization. What is extraordinary is how fast that gene therapy was constructed and deployed, which is a huge milestone for the industry. So hats off to you and the team. Maybe talk a little bit about how you fast-tracked the path to treatment.
Michelle Krueger: We developed it and gave it to her 14 months from the day of her diagnosis, and really ten months from the start of our gene therapy pursuit. We had to take some significant financial risk. We started manufacturing the drug before we had some very critical answers. We didn't know if it would work even in the cells. We didn't know if it was toxic. A lot of the pathways, you answer some of these critical questions before you would even consider developing the drug. But we decided we had to go as fast as we can for Elly.
We also entered into a grant with the University of Missouri to do our proof-of-concept and our toxicity studies. And, thankfully, the proof-of-concept studies checked out. And we saw in Elly's cells that the gene therapy could recover her cells.
We also then worked with Unravel in order to create a disease-induced tadpole model. And we saw that the MRNA could help recover the tadpoles.
Dan and I used to always say, "We're going to move as fast as we can. But once it's actually ready, we need to take a step back and say, 'Are we even going to give this to her?'" For the ten months, we didn't know the answer.
A lot of times in the development of gene therapy programs for N-of-ones or N-of-a-few is the parents go to an academic institution as a one stop shop. And that academic institution does the proof of concept. They outsource the toxicity study. They outsource the manufacturing. They write the IND. They hold the pen. And then they eventually dose your child.
We contracted directly with the manufacturer to develop the plasmids and then ultimately the vector. We contracted directly with University of Missouri to just do the proof-of-concept and the toxicity studies. We hired our own writer to write the IND along with Kathrin Meyer and others who were critical. But we acted as that central project manager. And I think that's really the main reason we could move so fast.
Stephanie Sirota: Tell us about whether there had been any investment in the space prior to your involvement.
Michelle Krueger: Part of the reason we could move so quickly is research had already been done, and other foundations came before us to fund that research.
So, we're incredibly grateful to the foundations and the parents that came before us that pushed that science.
We looked at it as a relay race where they then handed the baton to us, and we took that and went forward with translating it into a therapy.
Andrea, one of the main researchers out in Missouri that helped us with the entire lab at Missouri—they worked overtime to get us the proof-of-concept and the toxicity study results very quickly. Dr. Susan D'Costa, works at Genezen, and she kindly answered a call from Kat when we needed CMC expertise. And she helped me along the way with drug development.
And then the manufacturers, Andelyn and Charles River. They moved mountains. And I remember I called Andelyn at one point. I said, “You have to go faster. Her disease is progressing.”
And they did. They beat their own personal record for the fastest that they've ever developed a gene therapy. There are hundreds of people that worked on this that we are incredibly grateful for.
Becoming the first child to receive an IRF2BPL gene replacement therapy
Stephanie Sirota: That's unbelievable. So, take us to April 3rd, 2025. It's in New York City at high noon. You're at Weill-Cornell. And this is the moment—
Michelle Krueger: Yeah.
Stephanie Sirota: —that, you know, Elly will receive her treatment. Can you talk to us about that day?
Michelle Krueger: You're sitting there after months of pouring out your heart and soul and a lot of money into this treatment.
And this treatment could save her, or it could kill her.
And you don't know. And you're sitting there as a parent, and you're saying, “Should we really do this?”
In the hospital room, we handed her off. And we gave a final kiss. They said it was going to be about an hour. The one hour turned into three and a half or four hours. And I just had this kind of circular praying, and then going through the science, and then crying, and then wondering; “Are we doing the right thing?” Afterwards, Dr. Kaplitt comes out with Dr. Strauss, and they had big grins on their faces. And the second I saw that, I just knew that it went okay.
One of the complications of Elly's disease, is it's a neuro disease. So, you have to get the gene therapy into the brain, which is really hard to do. And then you have to keep it in the brain. They pulled out a picture, and that picture showed us that we got into the brain.
Stephanie Sirota: How's Elly doing?
Michelle Krueger: She's great. She's home. She's rolling around. She's very vocal. She's happy and playing with her siblings.
From a toxicity perspective, the first four weeks post-treatment are really critical to watch. You had to get into the brain. You also have to stay in the brain. And so, a lot of the gene therapy is naturally going to leak out and go to the liver. And so, you're watching the liver enzymes very carefully. You're watching blood tests very carefully. So that first month was really scary.
Thankfully, we didn't experience any toxicity impact. So her liver enzymes never got that high. Her blood results were relatively consistent. The reality is, we won't know if it worked for at least a year. Maybe two or three years.
Stephanie Sirota: Is that the time that it takes for the expression of the good gene to take over?
Michelle Krueger: Our doctors and our scientists have told us, “Don't even ask yourself, ‘Is it working?’ until at least a year.” We know we stayed in the brain because the liver enzymes never went up. And now it needs to integrate into her body.
Expanding the clinical trial for NEDAMSS
Stephanie Sirota: You have ambitions to open up this treatment to others. Can you tell me a little bit about that?
Michelle Krueger: The devastation early on got replaced with a sense of purpose. I was quite angry about it when I realized that this must be part of our purpose. But eventually, I understood that we are called to be part of this. And not just for Elly, but for all of the other kids with other neurodegenerative diseases. And I also believe that those who are given much, much is expected.
As a foundation, we're not done. We're focused on expanding the clinical trial for the gene therapy. Hopefully, to use the remaining doses in the most effective way to get it to be an approved drug. We never stopped our pursuit of drug repurposing and small molecule retesting and trying to see if there's already an FDA-approved drug that would actually help with our disease.
Stephanie Sirota: You sound like a biotech entrepreneur. (LAUGH) A lot of people are actually skeptical about biotech and worry about investing in this sector because of the volatility and the unknowns. But when it works, it changes lives. The companies that have delivered the biggest financial gains are the companies that have been able to produce great drugs that have left a real impact on patients. If you get that part right, then the returns follow. What do you think about the biotech industry?
Michelle Krueger: I didn't know much about it until the last 18 months. I remember at the beginning having conversations with anyone and everyone and just educating myself. When we think about biotech, they're developing techniques and approaches and drugs that, yes, might be for the masses, but then can be applied to the rare diseases. The rare diseases and the parents who are running it are driving the technology and the approaches that can then be used for the masses as well.
How to improve drug research and development
Stephanie Sirota: What would you like to see from a regulatory perspective?
Michelle Krueger: There's still this question with what does the FDA require for these n-of-a-few or these small clinical trials for ultra rare diseases? When I asked Dr. Meyer, “What would you do if your daughter was getting this treatment?” she said, “I might feel better if there was a larger animal that we tested it in because it's the first time it'll be in a human.” So we did our toxicity study in 150 mice and in five pigs. And the pigs are a lot of money and a lot of extra time.
So, I think trying to discuss as a community and align with the FDA on what is required for proof-of-concept, what is required for toxicity to move these therapies forward faster for the kids where time really matters and money and funding is very limited. We're all working towards this. I think having a roadmap for families and for foundations in these ultra rare situations to follow and to go down versus us all trying to recreate the wheel every time could really help move these therapies forward for kids who desperately need it.
Stephanie Sirota: What would you say to any parent who finds themself in your seat?
Michelle Krueger: There's times when things like this happen to you, and you might say, “Why me?”
And for me I really feel—I almost lost my life, and then I gained it. Over the last 18 months, I've found more joy. And I've found more hope. And I found good in the world. And I found people who are fighting for change.
The other thing I would say is keep fighting. Advocate for your child. Push the research. Push to translation of the research into treatments.
Stephanie Sirota: Thank you, Michelle. I wish that every day Elly gets stronger and healthier. And I wish all the luck and love in the world to you and your family.
Michelle Krueger: Thank you for having me.
Credits: The RTW podcast was produced and recorded by Devon Leaver at the RTW headquarters in New York, and edited by Dominique Guerra with Production Coordinator YingYu Lin. Executive Editorial Advisor was Stephanie A. Sirota, with Research Consultants Joe Katakowski and Nicole Litt, and Story Consultant Samantha Darris.
This interview was given by Michelle Krueger, Managing Director at Alvarez & Marsal Transaction Advisory Group, and the Co-Founder of Elly’s Team, and moderated by Stephanie Sirota, Chief Business Officer and Partner at RTW Investments, and President of the RTW Foundation.
Statements reflect RTW's views and opinions as of the date hereof and not as of any future date. All expressions of opinion are subject to change without notice and are not intended to be a forecast of future events or results. The views expressed by guests are their own and their appearance on the program does not imply an endorsement of them or any entity they represent.
This episode was recorded on June 11, 2025, and the clinical trial details discussed may have changed; please see https://ellysteam.org/ for the most current information on Elly’s case.
