The study was conducted on “mini-brains” which allowed the researchers to mimic the effects of the mutation within the gene and assess how the change might improve cognitive function.
Microscope images reveal significant differences in size and structure between brain organoids derived from a patient with Pitt-Hopkins syndrome (right) and a control (left) / Credit: UC San Diego.
A team of researchers has shown they can reverse an autism gene mutation by using gene therapy to give the gene a typical function that can lead to improved cognitive function. The results of the study, published in an article on Communication Natureshow how mutations within a gene called transcription factor 4 (TCF4) are linked to neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia.
The study was conducted on brain organoids, “mini-brains” that allowed researchers to mimic the effects of mutations within the gene and understand how mutations affect its function. Derived from skin cells taken from children with Pitt-Hopkins syndrome, a rare genetic condition that causes developmental delays, cognitive difficulties and seizures, these “mini-brains” had a TCF4 mutation that allowed researchers to to identify what would happen by using gene therapy to undo the mutation.
Reversing the Autism Mutation
Organoids with mutated TCF4 showed multiple developmental differences, including a reduced ability to create new neurons. A mechanism by which TCF4 might cause these effects was also discovered, showing that the mutation resulted in reduced expression of a key developmental gene. ” Even without a microscope, you might tell which brain organoid had the mutationSaid the study’s lead author, Alysson Muotri of the University of California San Diego School of Medicine, indicating how the organoids were structurally different due to mutated TCF4.
Microscopic images of developmental stages following immunostaining of brain organoids derived from patients with Pitt-Hopkins syndrome (PTHS) and parental control / Nature Communications
Compared to control organoids, the mutated organoids had an atypical structure that resulted in disruption of flow between neurons, which likely contributes to the cognitive impairments seen in ASD and similar disorders.
In an effort to improve impaired function, researchers have derived two alternative methods for increasing TCF4 levels. Both were successful, and the resulting organoids improved function, reversing the structural differences caused by Pitt-Hopkins syndrome. ” The fact that we can correct this gene and have the whole neural system restored, even at the functional level, is incredible. – this Muotri – although further studies are needed to verify whether altering TCF4 in a human model yields the same results. However, it strongly involves the gene and opens up new avenues to improve the quality of life of people with this disease.« .
