Brain Organoids, Moving Fragile X Research Forward

There are many ways research produces discoveries, and all of them include a process of steps that build on each other. When an exciting new avenue appeared with potential for Fragile X syndrome, FRAXA stepped up to fund it. We now see the results of this grant and are excited to share them with you.

The importance of different types of models have been shared and discussed over many years. We are now adding a “brain organoid” model to this group, and the potential behind it is really exciting. Emory’s Medical Xpress recently shared the findings of this new study.

Brain Organoids

Organoids are tiny, self-organized, three-dimensional tissue cultures grown from stem cells. They can be crafted to model much of the complexity of any organ — even the brain. A “brain organoid” model using human cells matches molecular and pharmacological aspects of Fragile X syndrome more closely than mouse models, Emory scientists report. The results were published recently in Nature Neuroscience.

FRAXA Grants, Making a Difference

With a $90,000 grant from FRAXA Research Foundation awarded over 2018-2019, Dr. Peng Jin and Dr. Juhnee Kang at Emory University began developing and analyzing Fragile X brain organoids to understand the disorder and identify treatment targets. In 2018 Dr. Jin shared with us, “One of the most exciting recent advancements in stem cell research has been the development of a new model that bridges the gap between mice and humans.” And he was right!

Thanks to this grant and other grants from FRAXA, we now have a deeper understanding of how brain organoids can help move Fragile X research forward.

Looking at the Details

Using reprogrammed skin cells donated by patients with Fragile X syndrome, scientists were able to mimic early stages of brain development in cell culture. The organoids correspond to a time 10 to 15 weeks after conception, when brain development is already perturbed by the Fragile X mutation. The organoids contain cells from just one part of the brain—the forebrain—and are not considered to display consciousness.

“We think brain organoids could be a powerful way to test therapeutic approaches and develop new compounds,” says Peng Jin, PhD, chair of human genetics at Emory University School of Medicine and co-senior author of the paper. “We don’t have the opportunity to look at this stage of development directly in the human brain.”

Compared with control organoids, the Fragile X organoids undergo accelerated differentiation and had fewer neurons that send inhibitory signals. The Fragile X neurons were hyperexcitable, arranged into layers more quickly and tended to migrate in disorganized patterns.

In the Nature Neuroscience paper, the researchers say that the changes in development in the human brain organoids are “more pervasive” than in mouse models. They show that loss of the Fragile X gene changed the activity of a larger number of genes in human brain cells, compared to mouse.

“These differences could be one of the reasons explaining why previous clinical trials were not successful,” says co-lead author Zhexing Wen, PhD,
The organoid model has also been used to study schizophrenia, Alzheimer’s disease, and the effects of Zika virus infection on early brain development.

Analyzing the human organoid cultures could also point to new drug targets. The researchers found many genes whose activity was altered in human organoids, but not Fragile X model mice.

Peng Jin Team at Emory University

Peng Jin, PhD, Principal Investigator, Yunhee Kang, PhD, FRAXA Postdoctoral Fellow, and Zhexing Wen, PhD, Co-Principal Investigator

Learn More with the FRAXA Seminar Series

If you missed it, Dr. Jin and Dr. Zhexing joined the FRAXA Seminar Series to discuss their organoid system and the phenotypes they found in Fragile X organoids. Dr. Jin also presented future directions for the newly funded Fragile X Center of Excellence at Emory University School of Medicine.


Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

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Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Explore Current Research Grants
Help Fund the Cure