CURE Epilepsy Discovery

Dishes of Discovery

Brain organoids grown from human cells offer insights into rare epilepsies

For most parents, their child’s fifth birthday marks a happy milestone. But for Tommy Pham, it is a bittersweet one for his son Raiden, who was born with a mutation in the UBA5 gene, which is critical for protein manufacture and processing within cells. As a result, Raiden cannot sit, walk, talk, or feed himself, and requires 24/7 care.

“He’s just lying there like he’s a baby, and he just turned five,” said Pham. “It’s a heartbreak. He’s supposed to be running, and playing with kids, or in school, but he can’t do any of that.”

When Raiden’s UBA5 mutation was diagnosed in 2021, only about 30 cases were being studied worldwide, a number that has only increased to 38 as of 2024. Since then, a handful of other impacted children have been identified in social media groups, with their conditions being debilitating and life-threatening: most have severe developmental delay, microcephaly, growth failure, and epilepsy.

Raiden’s uncertain future, combined with a lack of science surrounding this ultra-rare disease, spurred Tommy and his wife, Linda, to form the Raiden Science Foundation (RSF). The foundation networks with scientists and fundraises to support research on UBA5 Disorder, including building a patient network, creating animal models, and repurposing drugs, and creating a gene therapy.

Beyond Animal Models: Creating a Human “Brain in a Dish”

RSF is also banking on another method to directly study the effects of UBA5 mutations in human brain cells: brain organoids. Grown in the laboratory from skin cells, brain organoids are three-dimensional structures designed to mimic the cellular composition and architecture of the developing brain, allowing researchers to study the brain “in a dish” in the lab. They contain many types of brain cells, like neurons and astrocytes, which connect with each other as cells do in the human brain. Growing organoids involves a multi-step process of transforming skin cells into induced pluripotent stem cells (iPSCs), which have the potential to be made into any kind of cell in the body. Scientists can then direct the iPSCs to grow into different sorts of brain cells, that can be maintained and studied for over 100 days in laboratory dishes.

While brain organoids do not show the elaborate structures found in a human brain, they can be produced cost-effectively in large enough quantities to support different types of experiments, including those exploring potential drug or gene therapies. They also offer personalized insights, since they contain a patient’s entire genetic code, including their particular disease-related mutation. Because not all mutations of the same gene act alike, brain organoids could help pave the way toward personalized medicines.

While brain organoids can examine a mutation’s effects inside human cells, providing great insight to the drug discovery process, they cannot replicate the complicated consequences seen in a boy like Raiden. Thus, brain organoids complement, but do not replace, other experimental approaches such as development of animal models of genetic epilepsies.

“We’re helping to develop a platform and skills for other rare diseases, too. We want to fight for expanding knowledge, for research, for potential care in the future. The best way to describe it is that we’re fighting for hope.”

— Tommy Pham, Raiden’s Dad

This cutting-edge research is made possible by the generosity of our donors, like you. Thanks to your support, we can fund research to help Raiden and thousands of other children who are waiting for a cure.