.png)
4 months ago
9
Kyle: Five weeks before KJ was supposed to be born, and Nicole called me and said, we gotta go to the hospital. Like now, I don't know, six hours later, KJ was here. He was beautiful little boy, you know?
Nicole: Uh, little preemie
Kyle: Yeah. In that moment just seemed everything was fine. He was born on Thursday and then a doctor comes in Saturday morning and says, Hey, listen, there some things we saw that we didn't like. We were obviously very concerned, but we had no idea what we were in store for.
Rebecca Ahrens-Nicklas, MD, PhD: He was born at the adult hospital at the University of Pennsylvania and a very astute doctor at Penn actually checked his blood ammonia level, which is a marker for some of the metabolic diseases that we think about, and it was very, very high.
Kyle: We were sitting up there and one of the doctors came to us and said, we think we know what's wrong.
Your son is very sick, but the best place in the world for your child to be when he is very sick is next door. And I'll never forget that for the rest of my life.
Nicole: We would do absolutely anything for our kids. So it wasn't like a woe is me. It's, okay this happened to us. How are we going to support him?
So a urea cycle disorder is a type of metabolic disorder where you can't get rid or process parts of the protein that you take in your diet. This toxin ammonia builds up in your blood and then eventually will build up in your brain. If that went on unchecked for a day to two days, the patient would be at very high risk of death.
You Google CCPs one deficiency and it's either fatality rate or liver transplant.
Kyle: I bought a Jalen Hurts jersey like when he was first born. It hit me like he's probably never, might not wear that shirt, you know what I mean? Like I just.
Rebecca Ahrens-Nicklas, MD, PhD: In these really severe metabolic diseases of infancy, we know that we have to act quickly if we're gonna make a difference in the lives of these babies. We know that every day is really precious and matters in terms of keeping them healthy.
Kiran Musunuru, MD, PhD: So being on call in a, in a sense, doesn't just involve the clinical team anymore, involves a research team that's ready to work as quickly as possible to do some sleuthing in the lab and actually figure out, is there a fix for this genetic variant for the cause of the disease? The clock is ticking.
The sooner we can figure out a solution as to how to fix that genetic issue, the sooner we would be able to potentially make a therapy.
We had learned everything we needed to learn to actually get it all done in six months, in time to actually help him.
Rebecca Ahrens-Nicklas, MD, PhD: My biggest fear in all of this was giving false hope to a family, but we got to a point where we thought there might actually be a clinical team or a, a drug development team that could make a drug for KJ.
Kyle: Our, our child is sick. We either have to get a liver transplant or give him this medicine that's never been given to anybody before, right? I mean, what an impossible decision to make. Uh, I just think that we felt like this was the best possible scenario for a life that at one point we didn't know if he would be able to have.
Rebecca Ahrens-Nicklas, MD, PhD: KJ received the first infusion of his drug on February 25th, 2025. This is the first time that a patient has received a personalized gene editing drug.
Kiran Musunuru, MD, PhD: So when the infusion starts, most of the drug actually gets into the liver and is taken up by the cells almost immediately after it's gotten into the bloodstream.
CRISPR, a gene editor, enters the nucleus of the cell, and in this case we programmed it to go to the site of the genetic variant that is actually causing the disease in KJ.
Rebecca Ahrens-Nicklas, MD, PhD: The drug is really designed only for KJ, so the genetic variants that he has are specific to him. It's personalized medicine.
Kyle: Nobody knows if it's definitely gonna work, but I think just knowing that there's so much hard work and so much love, kind of going into all of this, it's important. It's important, Alex.
Nicole: What we saw in the first 10 days, we really could give him a lot more protein.
Kiran Musunuru, MD, PhD: Which ordinarily would be a problem and should cause the ammonia, the glutamine to go up and they didn't go up.
Rebecca Ahrens-Nicklas, MD, PhD: He's had quite a nice little growth spurt and we know that kids need protein to grow well. And so the fact that we've been able to give him more of that protein that he needs, I like to think has really helped him grow some nice chubby cheeks.
Photographer: Hey there buddy, what you doing down there? KJ!
Rebecca Ahrens-Nicklas, MD, PhD: We did realize, that while he could take more protein, he still needed his medications. [00:06:00] It seemed like the first dose was very well tolerated and safe, but that he would probably need more if it was gonna be more of a definitive therapy. Every day, we've made really nice forward progress to make me think that there might be a possibility where, he'll be able to be supported with very little medication or no medication.
Nicole: We've been operating in fight or flight
Kyle: Yes.
Nicole: For so long.
Kyle: Yes.
Nicole: That like it's starting to be like the light at the end of the tunnel. Fairly soon, if all goes well, all six of us will all be able to like, be at home, sit on the couch, watch a movie like we're planning for him to come home.
We thought it was important to give him a chance to show us what he could do.
Kyle: I just knew he was, he was ready. Like he was ready to fight.
Nicole: He's proven us, time and time again, how stubborn and spunky he really is.
Rebecca Ahrens-Nicklas, MD, PhD: We hope this is the first of many. I have so many patients with huge unmet need, right? So many patients where there's not a good option available for them.
But I really hope that 10 years from now, targeted personalized therapies are available for most of my patients. That would be the dream.
Kiran Musunuru, MD, PhD: For me, it's more than hope. It will happen. No, it will. I mean now that we have shown the way, we fully expect many metabolic physicians around the world to be, you know, excited about trying to do this for themselves.
And so I think this is the start of something.
Nicole: I don't think we'll ever be able to
Kyle: Express it.
Nicole: Yeah. Put into words how grateful we are for them.
Kyle: What I think about the most is him achieving things that were considered impossible. Man, the day he walks into like school with a book bag on and we like let him go at the door like you are gonna have to, I might have to take the day off that day.
