Gene editing saves baby and could help millions, scientists say

A baby born with a rare and dangerous genetic disease is growing and thriving after receiving an experimental gene-editing treatment made especially for him.

Researchers described the case in a new study, saying he is among the first to be successfully treated with a personalized therapy that seeks to correct a small but critical error in his genetic code that kills half of affected babies. While it may be some time before similar personalized treatments are available for others, doctors hope the technology could one day help the millions of people who have been left behind even as genetic medicine advances, given that their conditions are so rare.

“This is the first step toward using gene-editing therapies to treat a wide variety of rare genetic diseases for which there are currently no definitive medical treatments,” said Dr. Kiran Musunuru, a gene-editing expert at the University of Pennsylvania who co-authored the study published Thursday in the New England Journal of Medicine.

The baby, KJ Muldoon of Clifton Heights, Pennsylvania , is one of 350 million people worldwide with rare diseases , most of which are genetic. He was diagnosed shortly after birth with severe CPS1 deficiency, which some experts estimate affects about one in every million babies. These babies lack an enzyme needed to help remove ammonia from the body, so it can build up in the blood and become toxic. A liver transplant is an option for some.

Knowing KJ's chances, parents Kyle and Nicole Muldoon, both 34, were worried about losing him.

“We were, like, you know, weighing all the options, asking all the questions about liver transplant, which is invasive, or something that’s never been done before,” Nicole said.

“We prayed, talked to people, gathered information and ultimately decided this was the path we should take,” her husband added.

Within six months, the team at the Children’s Hospital of Philadelphia and Penn Medicine, along with their partners, had created a therapy to correct KJ’s defective gene. They used CRISPR, the gene-editing tool that earned its inventors the Nobel Prize in 2020. Instead of cutting the DNA strand like earlier CRISPR approaches, the doctors employed a technique that flips the mutated DNA “letter” — also known as a base — to the correct type. Known as “base editing,” it reduces the risk of unintended genetic changes.

It’s “very exciting” that the team created the therapy so quickly, said Senthil Bhoopalan, a gene therapy researcher at St. Jude Children’s Research Hospital in Memphis who was not involved in the study. “This really sets the pace and the standard for such approaches.”

In February, KJ received his first intravenous infusion of the gene-editing therapy, delivered via tiny droplets of fat called lipid nanoparticles, which are taken up by liver cells.

Although the room was buzzing with excitement that day, “he slept through the entire process,” recalled study author Dr. Rebecca Ahrens-Nicklas, a gene therapy specialist at CHOP.

After follow-up shots in March and April, KJ was able to eat more normally and recovered well from illnesses like colds, which can tax the body and worsen symptoms of CPS1 Syndrome. The 9½-month-old is also taking fewer medications.

Given his previous poor prognosis, “every time we see the smallest milestone he’s reaching — like a little wave or a rollover — that’s a big moment for us,” his mother said.

Still, researchers caution that it's only been a few months. They'll need to watch it for years.

“We’re still in the early stages of understanding what this drug may have done to KJ,” Ahrens-Nicklas said. “But every day, he’s showing us signs that he’s growing and thriving.”

Researchers hope what they learned from KJ will help other patients with rare diseases.

Gene therapies, which can be extremely expensive to develop, typically target more common disorders, in part for simple financial reasons: More patients potentially means more sales, which can help pay for development costs and generate more profit. The first CRISPR therapy approved by the U.S. Food and Drug Administration (FDA), for example, treats sickle cell anemia, a painful blood disorder that affects millions of people worldwide.

Musunuru said his team’s work — funded in part by the National Institutes of Health — showed that creating a personalized treatment doesn’t have to be prohibitively expensive. The cost was “not too far off” from the more than $800,000 for a liver transplant and related care, he said.

“As we get better and better at producing these therapies and shortening the timeline further, economies of scale will kick in and I expect costs to come down,” Musunuru said.

Scientists also won't have to redo all the initial work every time they create a personalized therapy, Bhoopalan said, so this research "sets the stage" for treating other rare conditions.

Carlos Moraes, a professor of neurology at the University of Miami who was not involved in the study, said research like this opens the door to further advances.

“When someone comes up with a breakthrough like this, it won’t be long” before other teams apply the lessons and move forward, he said. “There are barriers, but I expect those to be overcome in the next five to 10 years. Then the whole field will move as one, because we’re pretty much ready.”

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