Seven years after achieving a world-first in genomic medicine, Rady Children’s Health Orange County, formerly called CHOC, remains at the forefront of this revolutionary field.
Modifying the genetic code to treat disease, whether through in vivo gene replacement, ex vivo gene therapy (such as CAR T-cell therapy) or CRISPR-based genome editing, holds particular promise in pediatric medicine for one key reason: Many childhood diseases have a distinct genetic origin. Gene therapy offers the potential to intervene early and treat disease at its source, according to Nina Movsesyan, PhD, manager of Clinical Research Programs at Rady Children’s Health Orange County.
“In many rare genetic disorders, biological damage begins early and progresses relentlessly over time,” Movsesyan says. “Intervening during the pediatric stage allows us to preserve neurological function, mobility, organ function, vision and critical developmental milestones before irreversible injury occurs.”
In 2019, Rady Children’s Health Orange County helped advance the promise of genomic medicine by administering the world’s first successful gene therapy dosing for severe mucopolysaccharidosis type 1 (Hurler syndrome) in a 20-month-old boy. In subsequent years, the patient demonstrated sustained neurodevelopmental progress.
“This single-patient investigational new drug application generated critical safety data that allowed the trial sponsor to obtain FDA approval to lower the study’s dosing age from 6 years to 4 months,” Movsesyan says. “It was a monumental milestone for the entire field, as waiting until a child is 6 years old means the disease has already caused irreversible, progressive damage.”
Well-positioned to lead
Administering the experimental treatment for Hurler syndrome marked the start of Rady Children’s Health Orange County’s gene therapy work. In the years since, the hospital has built a reputation as a leading pediatric gene therapy center by:
- Adhering to the highest clinical trial governance and quality standards, thanks to close coordination between its Institutional Biosafety Committee and Institutional Review Board
- Assembling an integrated, multidisciplinary team of experts
- Maintaining accreditation for its laboratory operations from the Foundation for the Accreditation of Cellular Therapy
- Partnering with the California Institute for Regenerative Medicine (CIRM) Alpha Clinic at UC Irvine to enhance access to the latest gene therapies
“Administering gene therapies requires precise, synchronized support from neurosurgeons, interventional radiologists and specialized intensive care teams to ensure safety,” says Mei-Hui Wang, PhD, manager of Health Sciences Administration at Rady Children’s Health Orange County. “Our comprehensive, team-based model breaks down institutional silos to provide coordinated care from initial genomic diagnosis through complex delivery and long-term follow-up.”
Innovating tomorrow’s treatments
Rady Children’s Health Orange County physician-scientists continue to explore gene therapy’s potential to treat an array of diseases.
In 2023, the hospital’s affiliated blood disorders center became the first in the U.S. to administer a commercial gene therapy infusion for hemophilia A. The hospital’s exploration of gene therapy for Hurler syndrome continues, with five patients from the original trial currently enrolled in a long-term observational study. A project is underway to better understand the development of cardiovascular disease in patients with Hurler syndrome and mucopolysaccharidosis type IVA, and to stop the disease’s progression.
The Rady Children’s Health Orange County gene therapy clinical trials portfolio also includes investigations of:
- An in vivo base editing therapy to correct the R83C mutation in patients with glycogen storage disease type Ia.
- Genetically engineered ET140203 T cells in patients with liver cancer
“The protocol in the T-cell trial represents a massive shift in pediatric oncology,” says H. Harriet Chang, PhD, CCRC, supervisor and clinical research coordinator at the CIRM Alpha Stem Cell Clinic at UC Irvine and Rady Children’s Health Orange County. “Rather than relying solely on traditional chemotherapy, it uses genetically modified T cells to target the tumor.”
Preparing the next generation of investigators
To help ensure gene therapy science continues to thrive in the years ahead, Rady Children’s Health Orange County is building a deep bench of professionals. Currently, the hospital has three clinical research coordinator interns and three physician trainees enrolled in the UC Irvine Alpha Stem Cell Clinic Investigator Training Program.
“This program provides training in gene therapy oversight, safety monitoring and administration protocols, as well as hands-on participation in site initiation visits for upcoming trials,” Movsesyan says. “This ensures our site remains ahead of the complexity curve by establishing an efficient, highly trained operational pipeline.”
Forward-looking solutions
Fully realizing gene therapy’s immense promise requires overcoming key challenges, such as improving product precision, eliminating severe side effects and reducing manufacturing costs. Chang points to several methods Rady Children’s Health Orange County will use to solve these problems, including early detection of childhood diseases.
“We plan to drive earlier diagnoses through the seamless integration of advanced genomic sequencing and newborn screening,” she says. “Our metabolic team is collaborating with UC Irvine in the National Institutes of Health Undiagnosed Diseases Network and the Genomics Research to Elucidate the Genetics of Rare Diseases Consortium for emerging genomics technologies and analytics to accelerate their adoption in clinical practice.”
Additionally, Chang says, Rady Children’s Health Orange County will build multispecialty clinical and scientific teams to help drive therapies from discovery to clinical use. The hospital will work with data scientists, sponsors and patient advocacy groups to make gene therapies more widely available.
“Clinical research is a challenging, highly rigorous and often uncertain process,” Wang says. “The science involves navigating setbacks and failures. Only a small number of longitudinal efforts ultimately achieve commercial or therapeutic success. That is why deep persistence, long-term institutional investment and a mission-driven mindset are absolutely vital.”
Discover how the CHOC Research Institute is helping to transform pediatric medicine through more than 600 studies in dozens of specialties.
