The best way to impress friends at your next party may be to mention that scientists can grow miniature brain models from human stem cells. It might startle a few people, but once you explain how these tiny models help study neurological diseases and identify potential therapies, your social status may soar.
Modeling a rare disorder
Recently, a group at UC San Diego used human stem cells to model a rare neurological disorder and identified a drug molecule that might fix it. CIRM funded this work in part, and it was published today in the journal Molecular Psychiatry.
MECP2 duplication syndrome is caused by an extra copy of the MECP2 gene on the X chromosome. Because it is an X‑linked disorder, it occurs far more often in males. Extra MECP2 copies lead to reduced muscle tone, intellectual disability, impaired speech, seizures, and developmental delays. Current treatments only ease symptoms and do not cure the disease.
Using iPSCs
A UCSD group modeled MECP2 duplication syndrome using induced pluripotent stem cells from affected patients. They coaxed the iPSCs into the specific nerve cells harmed by the disorder. The diseased neurons behaved differently from healthy ones.
The affected neurons formed extra connections, which disrupted communication and normal function. Senior author Alysson Muotri called it an “over‑synchronization of the neuronal networks,” meaning the cells fired in unison.
After establishing this nerve‑cell model, the team screened a library of drug molecules and found one candidate that corrected the over‑synchronized activity.
Muotri explained the significance: this compound had never been considered for neurological disorders, and the team made progress quickly. In mice, similar work would have taken years and might not translate to humans.
The press release notes that Muotri’s team will continue preclinical studies using human stem‑cell‑based models, with the goal of moving into clinical trials.
After establishing a relevant nerve cell model of MECP2 duplication disorder, the group tested a library of drug molecules and identified a new drug candidate that rescued the diseased nerve cells from their “over-synchronized” activity.