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Better Understanding the Brain and Autism

As we’ve discussed at length in this space, there are two primary paths of research into the cause and possible cure of autism: the neurological approach and the genetic approach. The former camp argues that by studying and mapping the brain, we will find the key to what causes and what can possibly help treat autism. The genetic camp argues that autism is matter of one’s inherited DNA and thus have extensively mapped the genes and genetic combinations in individuals with autism.


Those in the neurological camp scored a big victory this week through a group of scientists who are hoping to discover the origins of autism by growing a large number of miniature proto-brains in a lab and studying them. The scientists are seeking to use reprogrammed skin cells to recreate organs that mirror the earliest versions of the human brain.


Through observing these “organoids”—clusters of brain cells smaller than one-tenth of an inch across—the researchers gained an unparalleled view into exactly how autism develops in the brain. What they found is that while a brain with autism is growing, it overproduces the brain cells that usually serve to mitigate the cacophony of neural activity in the brain.


When compared to a normally developing brain, the brain of a child who would go on to develop autism exhibited an imbalance between excitatory and inhibitory neurons. This makes for a subtle but powerful difference that may help researchers to pinpoint at least one bit of faulty writing that leads to autism’s behavioral symptoms.


The research was headed up by Yale physician and neurobiologist Flora Vaccarino and published last week in the journal Cell. Vaccarino and her colleagues also went on to report that when they suppressed a single gene that was abnormally active in organoids created from patients with autism, the researchers were able to fix the imbalance between neurons that suppress cellular impulses and those that amplify them.


However, according to Vaccarino, “The research has many hurdles to surmount before it might be used to diagnose and treat autism when a baby is still in utero, or just after birth. But the idea that their organoids may have given up a key secret of autism’s cause could give us something to focus on in developing treatments.”


While the insights into autism generated by the new research may be important, the methods used by Vaccarino and her colleagues are quite novel as well. First, the scientists used new lab procedures that have been shown to make skin cells revert to an undifferentiated form, like those harvested from embryos. The study authors then nudged the resulting stem cells to start the process of building a brain, and incubated the result for a month or more.


For at least 31 days, and as long as 100 days, they let reprogrammed brain cells divide, differentiate and grow. This gave the researchers a ringside seat from which to watch, in miniaturized form, the development of autistic and normal brains typical of a pregnancy’s second trimester.


By observing the brain during this crucial development period, Vaccarino argues that this might be the best way to solve the mystery of what causes autism. The next step for Vaccarino’s neurological approach is to build a wholly new brain from stem cells, an approach that is still merely a possibility. But her findings certainly bode well in terms of establishing a new method by which to better understand autism.