Successful Gene Editing Treatment for Rare Genetic Disorder
A baby born with a rare and serious genetic condition is doing well after receiving an experimental gene editing treatment tailored specifically for him.
The case was highlighted in a recent study, marking him as one of the first successful recipients of a custom therapy aimed at correcting a crucial error in his genetic makeup, which tragically claims the lives of about half of the babies affected. Although it might take time before similar personalized treatments become accessible, medical professionals are hopeful that this technology can benefit the millions who have rare conditions as advances in genetic medicine progress.
Dr. Kiran Musunuru, a gene editing specialist from the University of Pennsylvania and co-author of the study published in the New England Journal of Medicine, stated, “This is the first step towards using gene editing therapies to tackle a wide array of rare genetic disorders that currently have no definitive medical solutions.”
KJ Muldoon, a baby from Clifton Heights, Pennsylvania, is among the 350 million people globally living with rare diseases, most of them genetic. Shortly after birth, he was diagnosed with severe CPS1 deficiency, a condition estimated to affect roughly one in a million babies. This deficiency means the infants lack an essential enzyme for removing ammonia from the body, causing toxicity in their blood. A liver transplant is one potential treatment for some cases.
Understanding KJ’s precarious situation, his parents, Kyle and Nicole Muldoon, both 34, faced fears about losing him.
“We were weighing all the options, asking all the questions about a liver transplant, which is invasive, versus something entirely new,” Nicole recounted.
“We gathered information, prayed, and ultimately decided this was the best path for us,” Kyle added.
In just six months, the team from Children’s Hospital of Philadelphia and Penn Medicine, along with collaborators, developed a therapy meant to fix KJ’s faulty gene. They utilized CRISPR, the gene editing tool that earned a Nobel Prize in 2020. Instead of cutting the DNA as earlier methods did, the doctors adopted a technique that flips the incorrect DNA “letter” back to the correct type, known as “base editing,” thereby minimizing the risk of unintended genetic alterations.
Senthil Bhoopalan, a gene therapy researcher at St. Jude Children’s Research Hospital in Memphis who was not involved in the study, expressed excitement over the rapid creation of the therapy, calling it a significant milestone.
KJ received his first IV infusion of the gene editing treatment in February, delivered through small fatty droplets called lipid nanoparticles that transfer into liver cells.
During the process, “he slept through the entire thing,” Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP, recalled.
After receiving additional doses in March and April, KJ has shown improvements like eating more normally and recovering well from common illnesses, which can impact CPS1 symptoms. Now, at 9.5 months, he also requires less medication.
Reflecting on his previous prognosis, “Every small milestone, like a wave or rolling over, feels like a significant moment for us,” his mother shared.
However, researchers remind everyone that it’s only been a few months, and they’ll need to monitor KJ over the coming years.
“We’re still in the early stages of understanding the full impact of this medication on KJ,” Ahrens-Nicklas noted. “But each day, he’s demonstrating he’s growing and thriving.”
The hope is that insights from KJ’s case will aid others suffering from rare diseases.
Developing gene therapies is often costly, which typically leads researchers to focus on more prevalent disorders for financial viability—where larger patient bases can help offset costs. For instance, the first CRISPR therapy approved by the U.S. Food and Drug Administration treats sickle cell disease, a painful condition affecting millions globally.
Musunuru commented that their work, partly funded by the National Institutes of Health, demonstrates that creating custom treatments can be more affordable than perceived. The expenses are “not drastically different” from the costs associated with an average liver transplant.
“As we improve our methods and reduce the time needed for development, we expect costs to decrease further,” he predicted. Bhoopalan added that scientists won’t have to redo all initial work for each customized therapy, paving the way for potential treatments of various rare conditions.
Carlos Moraes, a neurology professor at the University of Miami not involved in the study, remarked that breakthroughs like this could lead to rapid advances in the field.
“Once there’s a significant development, other teams will quickly follow suit. Barriers exist, but I foresee these challenges being overcome in the next five to ten years, leading to collective progress in the field,” he said.
