New secrets of autism with human stem cells

New secrets of autism with human stem cells

A life-changing human disorder, ASD or more commonly known as Autism Spectrum Disorder, leaves behind a devastating disability. Clinical studies of multiple family histories and twins have shown that some cases of ASD are genetic. However, the majority do not fall into this category and occur suddenly intermittently or idiopathically in young children.

At the Hussman Institute of Autism (HIA) in the US, a team has been studying future methods related to the use of induced pluripotent stem cells, or iPSCs. When experimentally induced, a group of mature human stem cells from the skin or blood has the potential to differentiate into most cell types in the body. Since 2006, the process of induction and differentiation has been periodically upgraded. “One of the exciting aspects of working with iPSCs is that we can study autism in human neurons that have the precise genetic background of a particular autism,” said John P. Hussman, Executive Director of HIA.

“Mini-brains,” or organoids, derived from the iPS cells of ASD patients have been created by another Yale research group. It turns out that ASD mini-brains are made up of inhibitory neurons, a type of nerve cell that proliferates and blocks the production of a protein called FOXG1, then returns those neurons to their normal population numbers.

A CIRM-funded study led by Rusty Gage on a secondary stem cell model of ASD, which suggests new evidence for the initial neurodevelopmental abnormalities in ASD patients, was published in the Nature journal Molecular Psychiatry by the Salk Institute (USA) in collaboration with scientists at UC San Diego.

Under clinical conditions, Gage and a team of researchers tried to generate iPS cells, particularly from selected ASD patients, who had up to 23% faster brain growth in infancy. Under constant study, the researchers examined how iPS cells from these selected ASD individuals developed into brain stem cells. The next stage of growth transformed these brain stem cells into nerve cells. The entire growth trajectory was mapped and compared with that of healthy iPS cells from normal individuals.

By closely observing the procedure, the team quickly found a problem with the proliferation of brain stem cells to generate new nerve cells in the brain. The process is called neurogenesis. An excess of nerve cells was produced because the brain stem cells extracted from ASD-iPS cells exhibited additional neurogenesis compared to normal brain stem cells. The nerve cells were unable to send signals and establish a functioning transmission system. Due to the lack of synaptic connections between these additional neurons, their performance remained abnormal, representing an inability to be less effective compared to healthy neurons.

In this case, IGF-1, a drug currently in clinical trials for the probable treatment of autism, was used to treat the nerve cells. The team noticed a partial correction of the abnormal activity observed in the ASD neurons. According to a press release from Salk, the group plans to use the patient cells to study the molecular mechanisms behind the effects of IGF-1, particularly to examine changes in gene expression during treatment.

Gage's opinion is: "This technology allows us to generate views on the development of neurons that have been stubborn in the past. We are excited by the possibility of using stem cell methods to decipher the biology of autism and potentially search for new drug treatments for it." debilitating disorder.”

Inspired by Richa Verma