BOSTON — The father of a young boy with a rare disease reflected on an ordinary yet profound moment.
Last month, during the waning moments of a Sunday night football game, Eagles defensive tackle Jordan Davis made a crucial block against a Los Angeles Rams field goal attempt, securing a victory for Philadelphia. A jubilant Kyle Muldoon lifted his 1-year-old son, KJ, in front of the TV in their living room, causing the surprised child to cry. Apologizing to KJ, who was dressed in an Eagles jersey that Muldoon had bought him at birth, Kyle began to tear up himself.
“This is what we thought we would never experience,” he stated on Wednesday. At the STAT Summit, he and his wife, Nicole, shared their family’s journey from devastation to cautious optimism, ultimately finding themselves at the forefront of a significant medical story in 2025.
When KJ was born last August at the University of Pennsylvania, he arrived premature but appeared healthy. However, within days, he was transferred to the Children’s Hospital of Philadelphia (CHOP), where he was diagnosed with CPS1 deficiency, a rare urea cycle disorder that hindered his liver from processing ammonia, creating risk of severe brain damage or death. He was intubated and placed on dialysis.
KJ required a liver transplant for a chance at a typical life. Instead, a team of doctors presented him with an innovative treatment they wished to trial.
Six months later, with Nicole by his side in the hospital, KJ received an infusion of a gene editing therapy aimed at correcting the rare genetic error in his liver cells. Custom vials of treatment components were flown in from multiple states and Canada, each tailored specifically for KJ. Although the treatment hasn’t cured KJ, it has resulted in a significantly milder form of the disease and is being celebrated as a groundbreaking advancement in the pursuit of genomic medicine. This milestone has reignited discussions surrounding the safe and equitable expansion of personalized therapies.
By the conclusion of the couple’s presentation, many attendees were visibly emotional. Meanwhile, KJ beamed in a toddler-sized tuxedo, happily interacting with Kiran Musunuru, the geneticist who spearheaded the development of his treatment, all while sitting on the lap of Karen Ahrens-Nicklas, the physician who administered it.
Since the announcement of KJ’s successful treatment in May, the research team has been inundated with requests for help from families dealing with other rare diseases. While they respond to every inquiry, the reality remains that for most, there is little they can offer. The tailored drug for KJ corrected a single error in his DNA and, though it has yielded miraculous outcomes, the process demanded substantial resources, expertise, and investment that are not easily replicated.
Top researchers in Boston, including Ben Kleinstiver at Massachusetts General Hospital and David Liu at the Broad Institute, have contributed to refining the editing tool, utilizing a base editing version of CRISPR to ensure accurate DNA modifications. Fyodor Urnov from the Innovative Genomics Institute at UC Berkeley has collaborated with the teams at CHOP and Penn to establish an ambitious public-private partnership that harnesses resources from Aldevron, IDT, Acuitas Therapeutics, and the Jackson Laboratory.
“Scaling this technology is essential,” Ahrens-Nicklas emphasized. “In the U.S., we need to obtain approval so the drug can be reimbursed, allowing us to subsidize its use for patients nationwide. The technology exists; we just need the proper infrastructure to assess and deliver it.”
The duo has been working tirelessly over the past few months to put this plan into action. This winter, Musunuru announced their intention to petition the Food and Drug Administration to initiate a formal clinical trial open to patients suffering from seven distinct urea cycle disorders, as long as their mutations can be successfully addressed through base editing. They aim to develop a new “umbrella-of-umbrella” strategy, enabling individualized treatment assessments within a single trial framework. Following the treatment of five patients, they plan to advance to a Phase 3 trial, potentially paving the way for conditional approval of base editing as a foundational technology.
“Reaching that point is absolutely crucial,” Musunuru remarked. “It won’t solve all challenges, but without this step, we risk stagnating efforts to assist all the children who are in need.”
