The National Urea Cycle Disorders Foundation (NUCDF) is partnering with the Children’s Hospital of Philadelphia (CHOP) and other organizations on a new five-year federal grant of up to $38.9 million. The project aims to develop personalized gene-editing therapies for infants and children with severe, life-threatening liver-related genetic disorders, including urea cycle disorders.
It is funded by an award from the Advanced Research Projects Agency for Health (ARPA-H), the federal agency that supports medical “moonshots”—high-risk, high reward projects. Severe UCDs, especially those with neonatal onset, carry high rates of neurologic damage and early mortality. Existing treatments, including strict dietary management, medication, and liver transplant, can manage symptoms but cannot correct the genetic defect itself.
This project builds directly on the historic, individualized CRISPR gene-editing treatment of baby KJ Muldoon, who was born with severe CPS1 deficiency, a urea cycle disorder. That treatment was led by CHOP’s Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, of the University of Pennsylvania.
The new work will extend that approach into an early-stage clinical trial (called a Phase I/II trial) to treat additional patients with this new type of gene-editing treatment that can be tailored to each patient’s specific mutation. The researchers aim to build a flexible, repeatable system to accelerate development and, potentially, approval of these custom genetic treatments. According to a Stat+ article (subscription required), the CHOP team hopes to start a trial this year.
"We are so honored to partner with the NUCDF on this project," says Dr. Ahrens-Nicklas. "Their close connection to the urea cycle disorder community will help ensure our work reflects the needs and priorities of patients and families."
As a subaward partner, NUCDF will support the project through:
- Community engagement and education: Sharing study information with our extensive national patient network and increasing awareness through our communications channels.
- Stakeholder input: Providing patient and caregiver perspectives to help guide informed consent processes, outcome selection, and family-centered trial design.
“NUCDF has witnessed firsthand the devastating effects of severe UCDs — especially those with neonatal onset,” says Tresa Warner, NUCDF’s Executive Director. “This project offers a groundbreaking opportunity to address the root cause of severe UCDs and gives our community real hope for durable, transformative outcomes. We aim to help ensure the trial reflects the lived experience of patients and families. ”
The CHOP award was one of seven awards announced on July 9 by ARPA-H’s THRIVE program (Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines), which committed a total of up to $160 million over five years to the awardees.
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The National Urea Cycle Disorders Foundation (NUCDF) is a nonprofit organization dedicated to saving and improving the lives of children and adults affected by urea cycle disorders (UCDs) and raising awareness since 1988. Led exclusively by patients and families affected by UCDs, we are the driving force behind critical research to improve the understanding and management of UCDs, find new treatments, and ultimately create a cure. NUCDF serves as a lifeline to patients, families, and medical professionals worldwide seeking information, support, and hope. Visit www.nucdf.org or email info@nucdf.org.
