A baby born with rare and severe genetic disorders has thrived after receiving an experimental gene editing treatment tailored specifically for him.
The researchers outlined this case in a recent study, explaining that the infant received a custom therapy aimed at correcting a critical error in the genetic code, a condition that typically results in half of affected infants not surviving. Although it may take time for similar personalized therapies to become available for others, doctors remain hopeful that advancements in genetic medicine will allow millions to benefit, given the rarity of these conditions.
“This marks the initial step towards utilizing gene editing therapies. It addresses various rare genetic disorders that currently lack definitive medical treatments,” stated Dr. Kiran Musnoor, a gene editing specialist at the University of Pennsylvania, who co-authored the study published in the New England Journal of Medicine on Thursday.
KJ Muldoon, hailing from Clifton Heights, Pennsylvania, belongs to a global population of 350 million, the majority of whom are genetic. Shortly after birth, he was diagnosed with severe CPS1 deficiency, a condition estimated to affect roughly one in one million infants. These infants lack essential enzymes to eliminate ammonia from the body, leading to toxic levels in the bloodstream. While liver transplants may benefit some individuals, the prognosis remains dire.
Given KJ’s odds, his parents, Kyle and Nicole Muldoon, aged 34, were understandably worried about losing him.
“We evaluated all options and inquired about liver transplants,” his husband noted. “We prayed, consulted with others, gathered insights, and ultimately decided this was the path we wanted to pursue,” his wife added.
Within six months, the team at Philadelphia Children’s Hospital and Penn Medicine, together with their partners, developed a treatment designed to rectify KJ’s faulty genes. They employed GIRSPR, a technique developed by a Nobel Prize winner in 2020. Instead of cutting DNA strands like traditional CRISPR methods, doctors used a technique that inverts the “character” (or base) of mutated DNA into its correct form. Known as “base editing,” this approach minimizes the risk of unintended genetic alterations.
Gene therapy researcher St. Hill Boupalan from St. Jude Children’s Research Hospital in Memphis, who is not associated with the study, expressed excitement over the rapid development of the treatment. “This really establishes the pace and benchmark for similar approaches.”
In February, KJ received his first IV injection of gene editing therapy, delivered through small fatty droplets called lipid nanoparticles that are absorbed by liver cells.
The atmosphere was filled with anticipation that day, but “he slept through it all,” recalled Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP.
Following follow-up doses in March and April, KJ began to eat more normally and recovered from minor illnesses like colds. He has been on affordable medications for 9½ months.
Given his earlier bleak prognosis, “Every small milestone he achieves, whether it’s a wave or rolling moment, is significant for us,” his mother remarked.
However, researchers caution that it has only been a few months and long-term observations are crucial. “We are still at the beginning stages of understanding how this treatment has impacted KJ,” Ahrens-Nicklas noted. “Yet, every day he exhibits signs of growth and vitality.”
Researchers believe that insights gained from KJ’s case may inform treatment strategies for other rare diseases.
Gene therapy can be vastly expensive to develop, often prioritizing more common conditions for financial reasons. The treatment of more prevalent disorders opens avenues for greater patient numbers, facilitating recovery of development costs and generating profit. The first CRISPR therapy approved by the US Food and Drug Administration, for instance, targets sickle cell disease, a painful blood disorder affecting millions globally.
Musnoor affirmed that his team’s work — partially funded by the National Institutes of Health — demonstrates that custom treatments need not be prohibitively costly. He noted that the current expense is “not far off” from over $800,000, which is the average cost of a liver transplant and associated care.
“As we enhance these treatments and shorten the development time, we anticipate economies of scale, leading to cost reductions,” Musnoor explained.
Scientists also indicated that it won’t be necessary to repeat all initial tasks when creating new customized therapies, as Boupalan mentioned that this study “sets the groundwork” for addressing other rare conditions.
Carlos Mores, a professor of neurology at the University of Miami, who was not involved in the study, stated that such research paves the way for more advancements.
For other researchers to apply these lessons and move forward, “a breakthrough like this can lead to rapid progression,” he said. “There are hurdles, but I anticipate they’ll be overcome in the next five to ten years. With our readiness, the entire field can progress collectively.”
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Source: apnews.com