Breakthrough CRISPR Therapy Saves Infant with Rare Genetic Disorder in Just Six Months.

In a remarkable first for personalized medicine, a team of researchers at the Children’s Hospital of Philadelphia and Penn Medicine developed a custom CRISPR therapy for a newborn, KJ Muldoon, diagnosed with a rare and deadly genetic condition. The therapy was created and delivered in just six months, marking a record-setting pace and laying the groundwork for future rapid-response treatments for rare diseases.

KJ was born in August with CPS1 deficiency, a genetic disorder that prevents the body from properly clearing ammonia produced during protein digestion. This dangerous buildup of ammonia can cause severe organ damage, brain injury, and is often fatal in infancy. Approximately half of infants diagnosed with CPS1 deficiency do not survive early childhood. Traditional treatment involves a strict diet, medications to reduce ammonia, and in severe cases, liver transplants—an intensive and complex procedure, especially for infants.

Early symptoms were alarming: rigid muscles, extreme lethargy, and feeding difficulties. Fortunately, a collaboration led by Dr. Rebecca Ahrens-Nicklas and Dr. Kiran Musunuru set out to design a gene-editing solution tailored specifically to KJ’s genetic mutations. Genetic testing revealed KJ had inherited two different mutations in the CPS1 gene, one from each parent. The team chose to target the mutation previously linked to severe cases.

Using CRISPR base editing—a technology that allows precise alteration of a single DNA letter—they crafted a therapy aimed at correcting the underlying genetic defect. The gene-editing tools were delivered to KJ via lipid nanoparticles, tiny molecular carriers that naturally target the liver, where the CPS1 enzyme is produced. This method was chosen over traditional viral delivery to minimize potential immune reactions.

The therapy was tested in animal models before being submitted for emergency use approval to the U.S. Food and Drug Administration. Approval was granted just one week after submission. KJ received his first dose four days later, on February 25.

The treatment's design allowed it to be redosable, a cautious approach taken in light of previous setbacks in the field. In 2022, a 27-year-old man with Duchenne muscular dystrophy died after receiving a custom CRISPR treatment delivered via a virus, underscoring the risks involved.

Three doses into his personalized treatment, KJ is showing significant progress. He can now consume more protein, take lower doses of ammonia-lowering medication, and has achieved developmental milestones that once seemed out of reach. He can now sit upright and eat by mouth—achievements his parents had feared might never happen.

Although his care team stops short of calling it a cure, they are encouraged by the results. “It appears the treatment may have shifted his condition from a severe to a milder form,” said Dr. Ahrens-Nicklas. “But long-term monitoring will be essential.”

This case is detailed in a newly published study in The New England Journal of Medicine and was presented at the American Society of Gene & Cell Therapy annual meeting in New Orleans. Experts in the field, including Dr. Timothy Yu of Boston Children’s Hospital, called the approach a “comprehensive end-to-end process,” praising the team’s efficiency and safety precautions.

Dr. Yu, who pioneered a custom treatment for another rare condition using a different method called antisense oligonucleotides (ASOs), noted that while ASOs are more established in targeting diseases of the brain and spinal cord, CRISPR’s strength lies in its broader applicability to various genetic mutations.

One hurdle facing broader use of CRISPR is efficient and safe delivery to different organs. Current approved CRISPR therapies, such as Casgevy, involve removing cells from the patient, editing them externally, and then reinfusing them—a time-consuming and expensive process. In contrast, KJ’s therapy was administered intravenously, a method more viable for widespread application, especially for liver-based conditions like CPS1 deficiency.

Though the cost of developing KJ’s therapy wasn’t disclosed, it was comparable to that of a liver transplant—around $800,000. Much of the manufacturing support came as in-kind contributions from companies including Aldevron, Danaher, and Integrated DNA Technologies.

“This could have failed at any step,” said Fyodor Urnov, scientific director at UC Berkeley’s Innovative Genomics Institute, who collaborated on the study. “We’ve shown it’s possible to design and deliver a bespoke gene therapy fast enough to save a life.”

As CRISPR medicine continues to advance, the success of KJ’s case stands as a powerful proof of concept. “My hope,” Dr. Musunuru said, “is that one day, no child will have to suffer or die because of a typo in their DNA.”

Source:https://www.wired.com/story/a-baby-received-a-custom-crispr-treatment-in-record-time/

This is non-financial/medical advice and made using AI so could be wrong.