How tiny balls of human brain tissue are revealing the causes of childhood epilepsy — and possible treatments

September 23, 2026

Tuberous sclerosis complex, a leading genetic cause of early-onset epilepsy, is typically resistant to drugs, requiring surgical removal of brain lesions. A new study pinpoints a cause and potential new therapies.

In Helen Bateup’s UC Berkeley lab, graduate students and postdocs painstakingly nurture tiny balls of human brain cells for months and even years until they develop structures that mimic those in the brains of newborns shortly after birth.

By mutating genes in these so-called organoids, Bateup and her Berkeley team have now discovered a source of seizures in children with one of the most common forms of early-onset epilepsy — and have identified possible treatment strategies.

In a study appearing today (Sept. 23) in the journal Nature, the researchers report that hyperreactive astrocytes are one of the primary drivers of the inflammation that can cause seizures in these children. Luckily, experimental drugs exist that tamp down astrocyte-caused inflammation and may be able to lessen the seizures and help avoid the need for surgical removal of the areas of the brain involved. Astrocytes are one of three main types of glial cells in the brain and help to support and facilitate the transmission of signals through neurons.

Human brain organoids — each several millimeters across and floating in a nutrient liquid — contain only a few types of brain cells and are far from a real brain. But, unlike the flat layer of cells in a traditional cell culture, organoids develop and behave much like cells inside a living brain.

The inherited disorder, called tuberous sclerosis complex, is characterized by potato-shaped lesions in the brain that cause severe seizures often resistant to common antiseizure medications. The disease is also accompanied by debilitating symptoms in other parts of the body, including the heart, skin and kidneys.

The specific genetic cause of TSC’s tubers has been suspected for a long time: a child inherits a mutation in one allele, or copy, of a gene — either TSC1 or TSC2 — and then develops a random mutation in the other allele. With both copies of the gene defective, the child develops lesions that interrupt the brain’s electrical network. Often, these second mutations can occur independently in multiple regions of the brain, leading to numerous tuberous lesions.

An 89-day-old, human-derived brain organoid (close-up at right) with normal cells stained blue and mutated cells stained red
An 89-day-old, human-derived brain organoid (close-up at right) with normal cells stained blue and mutated cells stained red.
Helen Bateup/UC Berkeley

What wasn’t known is how mutations in these two genes, which regulate a major developmental and metabolic pathway throughout the body called mTOR, cause tuberous lesions in the brain. The assumption was that they were making neurons overreact, leading to seizures.

In the new study, Bateup, a Berkeley professor of neuroscience and of molecular and cell biology, and her colleagues show that a key consequence of these mutations is the generation of astrocytes in the brain that are hyperreactive from the moment they form. This suggests that abnormal astrocytes and other glial cells are not just a consequence of seizures — they actually cause the lesions themselves.

Read more at UC Berkeley News

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