Jojo’s Journey

Jojo was only 4 months old when she had her first seizure, which eventually led to a diagnosis of SCN8A epilepsy. This clinical-sounding abbreviation belies its heartbreaking reality: It’s a rare genetic mutation that can result in a severe, early-onset form of childhood epilepsy and developmental delays. And while traditional anti-seizure medications may initially control SCN8A symptoms, they can stop working or become less effective over time. Many children with the mutation don’t survive past early childhood. There is currently no cure.

Jojo’s parents — Patrick Ahearn, MD, transplant nephrologist in the Nephrology division at Stanford Department of Medicine, and his wife, Peggy Bui, MD, an internist — were devastated when they learned of their daughter’s diagnosis. But while networking with other families affected by rare diseases, they learned of the success story of Baby KJ — a baby with a previously untreatable, genetically inherited rare disease who was cured through personalized gene-editing therapy.  

“When I heard that a baby was cured through a technology that was developed from start to finish in six months, I thought, ‘Hope is alive; I have a purpose and mission,’” says Bui.

Ahearn and Bui determined they would move heaven and earth to find a cure for SCN8A. This would entail fixing the gene mutation through gene editing, a process that has never been done across the blood-brain barrier. They began by launching the “Hope for Jojo” campaign and forming a 501(c)(3) nonprofit called Rare Break — a reference to the “rare break” Jojo has in her genome and the “rare break” she needs to find a cure — to fundraise for this multimillion-dollar effort.

Gathering a Prestigious Research Team  

The search for a cure involves developing, testing, manufacturing, and delivering a gene therapy tailored to Jojo’s mutation. Ahearn and Bui enlisted three entities to work in tandem on this cutting-edge process. Through Baby KJ’s story, they learned about the Innovative Genomics Institute (IGI), whose role is to create the CRISPR gene editor (a genetic engineering tool used to modify DNA) and determine how to deliver it to Jojo’s cells.

“Initially we weren’t sure if the IGI would be able to work on our project because Jojo’s condition is so rare,” says Ahearn, “but we were fortunate enough to connect with the IGI’s director of therapeutic research and development, Fyodor Urnov, who has been supportive of Stanford’s own budding gene therapy program.” 

Once the IGI creates a gene editor proven to work with Jojo’s cells, The Jackson Laboratory will test its efficacy and safety on specially bred mice. Mice are biologically similar to humans and can be reprogrammed to express any number of genetic mutations, making them ideal for testing purposes. The Jackson Laboratory is using genome sequencing and genetic engineering to create mice that have the same SCN8A mutation as Jojo. “The work at The Jackson Laboratory has been going really well,” reports Ahearn. “Several mice were successfully born with the mutation, and these will be bred to create a larger cohort for testing.”

Playing a key role in the process is the Stanford Cardiovascular Institute Biobank (SCVI Biobank), founded by Joseph Wu, MD, director of the Stanford Cardiovascular Institute. The Biobank stem cell study team created the stem cells from Jojo’s blood that the IGI is using to test its gene editor.

Both The Jackson Laboratory and the IGI have helped secure some funding for these efforts, which they hope to scale for future research. The SCVI Biobank now has Jojo’s stem cells in its library of cell samples, which will be studied and shared with researchers around the world to advance scientific discoveries.

“We hope Jojo’s data from these experimental studies can help in making predictive models to create cures for rare diseases sooner, better, and faster,” says Bui.

It Takes a Village

Ahearn has received tremendous support throughout Jojo’s journey, starting in the Nephrology division.

Before Jojo was diagnosed and put successfully on anti-seizure medications, she was frequently hospitalized on an emergency basis, and Ahearn had to cut back on his clinical responsibilities, often at the last minute. Tara Chang, MD, division chief of Nephrology, notes, “Patrick’s colleagues were very supportive in covering for him and doing whatever they could so that he could be with Jojo. When something like this happens, we’re quick to step up and help each other. We care about Patrick and want to support him in any way possible.” 

“I received both clinical and emotional support from my colleagues,” Ahearn reflects. “Everyone has been so gracious and gone above and beyond. I couldn’t work in a better place.” 

Nephrology was not the only division stepping up for Ahearn — he made helpful contacts throughout the Stanford family. And each outreach seemed to lead to another promising connection in Jojo’s journey.

“I’m grateful to so many at Stanford,” says Ahearn. “Vivek Bhalla, MD, who is doing a lot of work with gene therapy and has industry contacts that might be able to help later in the process, encouraged me to keep Euan Ashley, MD, PhD, involved in our journey. Dr. Ashley is collaborating with the IGI, among other expert teams, and encouraged me to reach out to Mary Leonard, MD, chair of pediatrics, who supports efforts involving curative pediatric genetic therapies. Rebecca Levy, MD, a pediatric neurologist, introduced me to Dr. Wu’s lab, whose research team is generating the stem cells. Xixi Zhao, MD, put me in touch with a company studying a new anti-seizure medicine that we might be able to get early access to. The level of interest and eagerness to help is overwhelming.”