A Quiet Revolution: How Pigs Are Bringing Hope to CDKL5 Families 🐷

🐷 In the shadowed corners of medical research, where hope battles against heartbreaking genetic disorders, a quiet revolution is unfolding at the National Swine Resource and Research Center (NSRRC) and the National Swine Testing Center (NSTC). These two NIH-funded swine centers are located at the University of Missouri, led by Dr. Kiho Lee (NSRRC) and Dr. Jonathan Green (NSTC).

This work began with a request from Dr. Cecelia Lo, Distinguished Professor & F. Sargent Cheever Chair of Developmental Biology at the University of Pittsburgh. Dr. Lo asked the NSRRC to develop a pig model with alterations in the CDKL5 gene that could mimic CDKL5 Deficiency Disorder (CDD). The NSRRC, which supports the scientific community by creating biomedical pig models, quickly took on the challenge and began characterizing the model alongside Dr. Lo and her team. The NSTC now plays a vital role in testing the safety and effectiveness of delivering gene-editing therapies in pigs. With both centers based at the University of Missouri, the process of creating animal models and testing new treatments is highly streamlined.

For families of children with CDKL5 Deficiency Disorder (CDD) — a devastating neurological rare disease that robs infants of developmental milestones and causes relentless epilepsy and delays — time is the fiercest enemy. Yet the journey toward treatment is long, costly, and often overlooked by major pharmaceutical companies.

Before any gene therapy can reach patients, it must pass rigorous preclinical testing. Research typically begins in small animals and cell systems, but large-animal models are needed to more accurately reflect human brain development and disease. Pigs are especially valuable because their brain size and structure are much closer to humans, making them critical models for understanding complex neurological conditions. Until now, creating such a model for CDKL5 had proven nearly impossible because of the severity of the disorder. Thanks to Dr. Lee, Dr. Green, Dr. Lo, and their teams, researchers now have a living system that mirrors the seizures, developmental challenges, and neurological features of human CDD — opening an unprecedented opportunity to test therapies in a meaningful way.

This breakthrough has been strengthened through collaboration with the Child's Cure Genetic Research Foundation, co-founded by Jainu Jogani, who is leading efforts to bring CDKL5 gene replacement therapy to the clinic. Together with Missouri's expertise, the partnership is advancing the use of imaging technologies like MRI and PET to track disease progression and treatment response in the same animals over time — reducing the need for animal sacrifice while deepening insights into long-term therapy effectiveness. Sustaining and expanding these efforts depends on continued funding, and thanks to the dedication and vision of Jainu Jogani, this critical work is moving forward with urgency and purpose.

The implications are profound: for the first time, researchers can test gene therapy for CDKL5 in a large-animal model that closely mimics the human condition — including seizures, learning difficulties, and social impairments — measure its long-term effects, and accelerate the path to clinical trials.

In the race against life-threatening rare diseases like CDKL5 — where many children have tragically lost their lives before reaching their teenage years — speed is everything. Thanks to the University of Missouri and committed partners, the field finally has the tools to close the gap and bring real hope to families who have been told there is none.