A baby born with a is growing and thriving after getting an experimental made just for him.
Researchers described the case in a new study, saying he鈥檚 among the first to be successfully treated with a custom therapy that seeks to fix a tiny but critical error in his genetic code that kills half of affected infants. Though it may be a while before similar personalized treatments are available for others, doctors hope the technology can someday help the millions left behind even as genetic medicine has advanced because their conditions are so rare.
鈥淭his is the first step towards the use of gene editing therapies to treat a wide variety of rare genetic disorders for which there are currently no definitive medical treatments,鈥� said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert 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, estimated by some experts to affect around one in a million babies. Those infants lack an enzyme needed to help remove ammonia from the body, so it can build up in their blood and become toxic. A liver transplant is an option for some.
Knowing KJ鈥檚 odds, parents Kyle and Nicole Muldoon, both 34, worried they could lose him.
鈥淲e were, like, you know, weighing all the options, asking all the questions for either the liver transplant, which is invasive, or something that鈥檚 never been done before,鈥� Nicole said.
鈥淲e prayed, we talked to people, we gathered information, and we eventually decided that this was the way we were going to go,鈥� her husband added.
Within six months, the team at Children鈥檚 Hospital of Philadelphia and Penn Medicine, along with their partners, created a therapy designed to correct KJ鈥檚 faulty gene. They used CRISPR, the gene editing tool that in 2020. Instead of cutting the DNA strand like the first CRISPR approaches, doctors employed a technique that flips the mutated DNA 鈥渓etter鈥� 鈥� also known as a base 鈥� to the correct type. Known as 鈥渂ase editing," it reduces the risk of unintended genetic changes.
It鈥檚 鈥渧ery exciting鈥� that the team created the therapy so quickly, said gene therapy researcher Senthil Bhoopalan at St. Jude Children鈥檚 Research Hospital in Memphis, who wasn鈥檛 involved in the study. 鈥淭his really sets the pace and the benchmark for such approaches.鈥�
In February, KJ got his first IV infusion with the gene editing therapy, delivered through tiny fatty droplets called lipid nanoparticles that are taken up by liver cells.
While the room was abuzz with excitement that day, 鈥渉e slept through the entire thing,鈥� recalled study author Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP.
After follow-up doses in March and April, KJ has been able to eat more normally and has recovered well from illnesses like colds, which can strain the body and exacerbate symptoms of CPS1. The 9 1/2-month old also takes less medication.
Considering his poor prognosis earlier, 鈥渁ny time we see even the smallest milestone that he鈥檚 meeting 鈥� like a little wave or rolling over 鈥� that鈥檚 a big moment for us,鈥� his mother said.
Still, researchers caution that it鈥檚 only been a few months. They鈥檒l need to watch him for years.
鈥淲e鈥檙e still very much in the early stages of understanding what this medication may have done for KJ,鈥� Ahrens-Nicklas said. 鈥淏ut every day, he鈥檚 showing us signs that he鈥檚 growing and thriving.鈥�
Researchers hope what they learn from KJ will help other rare disease patients.
Gene therapies, which can be extremely expensive to develop, generally target more common disorders in part for simple financial reasons: more patients mean potentially more sales, which can help pay the development costs and generate more profit. The first CRISPR therapy , for example, treats sickle cell disease, a painful blood disorder affecting millions worldwide.
Musunuru said his team鈥檚 work 鈥� 鈥� showed that creating a custom treatment doesn鈥檛 have to be prohibitively expensive. The cost was 鈥渘ot far off鈥� from the $800,000-plus for an average liver transplant and related care, he said.
鈥淎s we get better and better at making these therapies and shorten the time frame even more, economies of scale will kick in and I would expect the costs to come down,鈥� Musunuru said.
Scientists also won't have to redo all the initial work every time they create a customized therapy, Bhoopalan said, so this research 鈥渟ets the stage鈥� for treating other rare conditions.
Carlos Moraes, a neurology professor at the University of Miami who wasn't involved with the study, said research like this opens the door to more advances.
鈥淥nce someone comes with a breakthrough like this, it will take no time" for other teams to apply the lessons and move forward, he said. 鈥淭here are barriers, but I predict that they are going to be crossed in the next five to 10 years. Then the whole field will move as a block because we鈥檙e pretty much ready.鈥�
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Laura Ungar, The Associated Press
