A study published in Nature Communications by a scientist team from University of California San Diego School of Medicine looked into gene therapy and how it may be able to reverse the effects of autism-linked mutation.
The research used human brain organoids in order to figure out how a genetic mutation linked to a severe form of autism can disrupt neural development.
That being said, by using gene therapy tools, they managed to recover the gene’s function, rescuing neural function and structure effectively.
Quite a few neuropsychiatric and neurological diseases, autism and schizophrenia included, have been linked to an essential gene in brain development known as Transcription Factor 4.
These factors’ role is regulating whenever other genes get turned on and off which means that their presence or lack of presence can lead to major changes in the development of the embryo.
Regardless, not a lot is known as far as what happens to the brain when TCF4 mutates is concerned.
As a result, the scientist team focused on an Autism Spectrum Disorder caused by TCF4 mutations known as Pitt-Hopkins Syndrome.
This genetic condition causes serious motor and cognitive disabilities in kids who have it and they are also usually non-verbal.
Using mouse models for the human disorder, the researchers used stem cell technology and converted skin cells into stem cells, only to then develop them into 3D “mini-brains.”
Initially, they noticed that the mini-brains had many functional as well as structural differences when compared to the TCF4-mutated samples and their controls.
Senior study author Alysson R. Muotri explained that “Even without a microscope, you could tell which brain organoid had the mutation.”
The team also tested two gene therapy strategies in order to recover the functional gene in brain tissue and both methods were able to increase TCF4 levels successfully, therefore correcting the Pitt-Hopkins Syndrome phenotypes at all scales, be it cellular, molecular or electrophysiological.
Muotri went on to mention that “The fact that we can correct this 1 gene and the whole neural system reestablishes itself, even at a functional level, is amazing,” noting that the genetic interventions all happened at the prenatal stage of brain development as opposed to what usually happens where kids get diagnosed and treated years into their condition.
The president of the Pitt Hopkins Research Foundation, Audrey Davidow praised the results, saying that “What is truly outstanding about this is that these researchers are going beyond the lab and really working hard to make these findings translatable to the clinic. It is so much more than a stellar academic paper; it is a true measure of what well practiced science can accomplish to change human lives for the better.”