How personalized brain organoids could help us demystify disorders

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"The researchers also grew organoids using cells from a 25-year-old woman and a 5-year-old girl with Rett syndrome, a [rare genetic neurological and] developmental disorder marked by seizures, autism and developmental lags. Rett syndrome is thought to be caused by changes in a gene called MECP2, mutations that the lab-grown organoids carried as well.

These organoids looked like those grown from healthy people, but behaved differently in some ways. Their nerve cells fired off signals that were too synchronized and less varied. Some of the brain waves these organoids produced are reminiscent of a brain having a seizure, in which a bolus of electrical activity scrambles normal brain business.

With organoids carrying Rett syndrome mutations, scientists can better understand the syndrome and even begin to test possible treatments. ..."

From the abstract:

"Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery."

How personalized brain organoids could help us demystify disorders | Science News Clumps of brain cells made from people with Rett syndrome had abnormal electrical activity

Identification of neural oscillations and epileptiform changes in human brain organoids (no public access, but the article above contains a link to the PDF file)