StemoniX Develops 3D Human Microbrains of Rett Syndrome to Accelerate Therapy Development

Three-dimensional microbrains built in the lab using stem cells from Rett syndrome patients can become a new model to study the disease, neuroscientists say. This can help identify new therapeutic compounds to treat Rett syndrome and accelerate therapy discovery for other neurodevelopmental disorders.

The study, “3-Dimensional Human Cortical Neural Platforms for Drug Discovery in Neurodevelopmental Disorders” was presented by Cassiano Carromeu, PhD, lead neuroscientist at StemoniX, at the SLAS2019 Conference, Feb. 2–6 in Washington, D.C.

Modeling the complex interactions of the central nervous system (CNS, brain and spinal cord) in the lab has been a herculean task. “Scientists have long sought to develop effective in vitro models of the human central nervous system; however, the unique structural organization that enables the CNS to perform its complex functions is not easily reproducible,” Ping Yeh, co-founder and CEO of StemoniX, said in a press release.

“This research signals an important advancement in finding new therapeutics for diseases of the central nervous system,” he added.

Researchers at StemoniX have now built 3D microbrains — called microBrain 3D — that grow like small spheroids and are composed of cortical neurons and astrocytes, a group of star-shaped cells that provide neurons with energy and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation.

The team used induced pluripotent stem cells (iPSCs) from people with Rett syndrome. These cells derive from either skin or blood cells that have been reprogrammed back into a stem cell-like state, which allows for the development of an unlimited source of any type of human cell needed for therapeutic purposes.

They were then able to build microbrains that recapitulate features of the disease. Specifically, these microbrains developed a neural network that presented with abnormal calcium signaling, which translates into abnormal activity of nerve cells. The electrical activity of neurons in the brain is maintained by channels that allow the movement of substances such as calcium, potassium, and sodium in and out of nerve cells.

Researchers then used their newly established 3D microbrains to screen a library of 296 compounds known for their ability to alleviate some symptoms of Rett syndrome. This can allow scientists to discover potential therapeutic approaches at a faster pace and lower cost.

“StemoniX developed microBrain 3D to address this significant opportunity, and we believe the data presented at SLAS2019, particularly our ability to generate a functional in vitro Rett Syndrome model, exemplify the technology’s potential to dramatically change the current drug discovery paradigm for neurodevelopmental disorders and other neural diseases,” Ping said.