Autism: Gene therapy reverses the effect of a gene  

It saved neurological structure and function

San Diego School of Medicine scientists have discovered changes in the brain’s neurological structure that may underlie autism spectrum disorders, thanks to lab-grown brains based on human cells. In fact, the researchers were able to restore lost genetic functions through two different gene therapies. These developments give hope to millions that one day we will have new ways to improve the lives of people with autism.

Pitt Hopkins syndrome is a neurodevelopmental condition caused by a mutation in a gene called TCF4. It belongs to the autism spectrum because of the severe effects on movements and sensory organs. In addition, the TCF4 gene is also linked to other forms of autism and neurological disorders, including schizophrenia.

Despite the important role of the gene in the development of our brain, we know very little about its mechanisms and its mutations. Research puts the gene under the microscope, studying it in an environment as close as possible to what is ethically acceptable. Pitt Hopkins volunteers’ skin cells were reprogrammed as stem cells, which in turn formed the basis for a brain-like mass called a cortical organelle . These organelles are a simplified version of a real brain and cannot perform all the functions that the brain can, but they help scientists study various features of the brain.

The researchers therefore found that the mutation of the TCF4 gene caused a decrease in the number of neurons and a drop in their activity. By artificially supporting the signaling with drugs, the researchers were able to restore at least some of the neurological and electrical activity in the organelles.

Genetic correction of the TCF4 mutations even reversed its effects, with the organelles functioning like those of the control group.

The fact that we can correct one gene and the entire neural system even returns to functional levels is really impressive.

However, the day when we will have a truly effective treatment is still far away, since the organelles being non-functional brains, leave a lot of room for overlooked factors that can complicate the process.

For these children and their parents, any improvement in their motor functions and quality of life is worth the effort.

The research was published in Nature Communications .