This year has seen a lot of studying neurological disease on the cellular level using brain organoids. Scientists used brain organoids—or clumps of cells that in many ways mimic the human brain—to study the connection between the eyes and the brain, for example. Now, a team of scientists from the University of Cambridge has used the “mini brains” to analyze serious maladies like lateral sclerosis and even dementia. Something they were able to do thanks to stem cells from patients themselves.
Design Taxi reported on the new use case for brain organoids, a.k.a. “cerebral” organoids. As the name implies brain organoids are very similar to human brains. (So much so that some scientists even equate them to the brains of ten-week-old human embryos.) Scientists often produce the miniature brains by reverting human skin cells back to their stem cell state. They subsequently culture the stem cells as 3D models that contain several types of nerve cells. As well as anatomical features that are approximately similar to regions of the cortex.
In this instance the scientists used stem cells derived from patients suffering from amyotrophic lateral sclerosis, or ALS. As well as frontotemporal dementia, or FTD. The scientists then used the cells to grow organoids (like the one in the unrelated image below) into clumps roughly the size of peas; critically, keeping the pea brains alive for hundreds of days. A feat in this area of research.
“Neurodegenerative diseases are very complex disorders that can affect many different cell types and how these cells interact at different times as the diseases progress,” Dr. András Lakatos said in a press release. The neuroscientist and senior author of a paper outlining this effort in the journal Nature Neuroscience added that “To come close to capturing this complexity, we need models that are more long-lived and replicate the composition of those human brain cell populations in which disturbances typically occur, and this is what our approach offers.”
Using this approach Lakatos and his colleagues were able to observe changes in the organoids’ cells. They noticed, for example, how cellular stress at an early stage damages DNA and the transcription of proteins. They were also able to demonstrate that a drug—GSK2606414—was able to heal some of the damage by diminishing the buildup of toxic proteins. The scientists say the goal now is to find out of this damage begins as soon as somebody is born. As well as if other potential drugs can prevent or slow the progression of ALS and FTD. Only time, and more mini brains, will tell.
Feature image: University of Cambridge