A baby born with rare and perilous genetic disorders has flourished thanks to an experimental gene editing treatment tailored specifically for him.

Researchers detailed the situation in a recent study, explaining that he initially received a personalized therapy aimed at rectifying a critical genetic flaw responsible for the death of half of affected infants. While wider availability of similar tailored treatments may take time, doctors remain optimistic. They believe that as genetic medicine advances, it can assist millions still facing rare conditions.

“This represents a pivotal advancement in gene editing therapy, addressing various uncommon genetic disorders that currently lack effective medical solutions,” stated Dr. Kiran Musnoor, a gene editing specialist from the University of Pennsylvania and co-author of the study recently published in the New England Journal of Medicine.

KJ Muldoon, from Clifton Heights, Pennsylvania, is among the 350 million people globally grappling with genetic issues. Shortly after birth, he was diagnosed with severe CPS1 deficiency, a condition estimated to affect about one in a million infants. These babies are unable to produce the enzymes required to eliminate ammonia from their systems, leading to toxic accumulation in the bloodstream. For some, liver transplants are a viable option.

Understanding KJ’s circumstances, his parents, Kyle and Nicole Muldoon, aged 34, were understandably anxious about the possibility of losing him.

“We evaluated all available options and posed numerous questions about potential liver transplants,”

“We prayed, consulted others, collected information, and ultimately decided this was the best path forward,” Kyle added.

In just six months, the team at Philadelphia Children’s Hospital and Penn Medicine, in collaboration with their partners, devised a treatment aimed at correcting KJ’s faulty genes. They utilized GIRSPR, a technique for which the inventor received the Nobel Prize in 2020. Rather than cutting DNA strands like earlier CRISPR methods, doctors implemented a technique that alters the “letter” (or base) of the mutated DNA, transforming it into the correct version. This approach, known as “base editing,” minimizes the chances of unintended genetic alterations.

St. Hill Boupalan, a gene therapy researcher at St. Jude Children’s Research Hospital in Memphis, who was not part of the study, remarked that it is “incredibly thrilling” how quickly the treatment was developed. “This genuinely establishes a new benchmark for this approach.”

In February, KJ received his first IV injection of the gene editing therapy, delivered through small fatty droplets called lipid nanoparticles, which are absorbed by liver cells.

The atmosphere was filled with excitement on that day, but “he slept through the entire procedure,” Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP, recalled.

Following subsequent doses in March and April, KJ began eating normally and recovered well from minor illnesses, such as colds. He has been on economical medications for the past 9½ months.

Given his grim prognosis initially, “each small milestone he reaches feels monumental for us,” his mother expressed.

Nonetheless, researchers caution that only a few months have passed. They need years of observation.

“We’re still in the early stages of comprehending the effects this drug has had on KJ,” Ahrens-Nicklas stated. “However, he demonstrates signs of growth and well-being daily.”

Researchers are hopeful that KJ’s case could provide insights beneficial to patients with other rare diseases.

While developing gene therapies can be tremendously pricey, they often focus on more prevalent conditions for financial viability. A broader patient base can enhance sales, assisting in covering development costs and yielding more profit. For instance, the first CRISPR therapy approved by the US Food and Drug Administration addresses sickle cell disease, a painful blood disorder impacting millions worldwide.

Musnoor mentioned that his team’s efforts—partially funded by the National Institutes of Health—demonstrate that customizing treatments does not necessarily have to be prohibitively expensive. He indicated that costs are “not far off” from the $800,000 average for a liver transplant and associated care.

“As we continue to develop these treatments and shorten the timeframes, we anticipate economies of scale, which will drive costs down,” Musnoor noted.

Scientists also emphasized that it isn’t necessary to repeat all initial steps each time a customized therapy is created, as noted by Boupalan. This study “paves the way” for other rare condition treatments.

Carlos Mores, a neurology professor at the University of Miami who was not involved in the study, stated that such research paves the way for future advancements.

For other teams to apply insights and move forward, “breakthroughs like this can spur progress quickly,” he remarked. “Though there are challenges ahead, I predict we will overcome them in the next five to ten years, leading the entire field to advance collectively.”