The genetic mutation in autism can be reversed through gene therapy

The study was conducted on “small brains” which allowed the researchers to mimic the effects of the mutation within the gene and assess how the change might improve cognitive function.

Micrographs reveal significant differences in size and structure between brain organelles derived from a patient with Pitts Hopkins syndrome (right) and a control (left) / Credit: University of California, San Diego.

A team of researchers has shown that they can reverse the genetic mutation of autism by using gene therapy to give the gene a typical function that could improve cognitive function. The results of the study published in an article dated Connecting with natureShow how mutations within a gene called transcription factor 4 (TCF4) are associated with neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia.

The study was conducted on brain organelles, “mini-brains” that allowed researchers to mimic the effects of mutations within a gene and to 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 “little brains” had the TCF4 mutation that allowed researchers to determine what might happen by using gene therapy to undo the mutation.

Reversing the autism mutation

Organisms with mutant TCF4 showed multiple developmental differences, including a reduced ability to form new neurons. A mechanism was also discovered by which TCF4 could cause these effects, demonstrating that the mutation reduced the expression of a key gene in development. ” Even without a microscope, you can tell which brain organelle has the mutationThe study’s lead author, Alison Muotri of the University of California San Diego School of Medicine, said, noting how the organelles were structurally different due to the mutant TCF4.

Micrographs of developmental stages after immunoblotting of brain organs derived from Pitt Hopkins syndrome (PTHS) patients and parental control / Nature Communications

Compared with the control organelles, the mutant organoids had an atypical structure that disrupted interneuronal flow, likely contributing to the cognitive impairments seen in ASD and similar disorders.

In an effort to improve the impaired function, researchers have derived two alternative ways to increase 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 restore the entire nervous system, even at a functional level, is incredible. – says Motri – Although more studies are needed to verify whether alteration of TCF4 in a human model leads to the same results. However, it includes the gene powerfully and opens up new ways to improve the quality of life of people with this disease.“.