For decades, studies have focused on modeling the disorder in mice, or studying isolated human brain cells, but there are no perfect models of the complexity of the human brain.
In this regard, scientists at the American Scripps Research Institute used stem cells taken from patients suffering from a rare form of autism spectrum disorder, to grow “mini-brains” (organoids) with the aim of studying this disorder in more depth.
The research team focused on MEF2C deficiency syndrome, a rare form of autism spectrum disorder. (In healthy brains, neural stem cells develop into neurons that send and receive messages. But in brains affected by MEF2C deficiency syndrome, the stem cells tend to turn into glial cells, leading to an imbalance between neurons and glial cells.)
The researchers used skin cells isolated from patients, turned them into human stem cells, and then cultured them to form “mini-brains” (organoids) to study how brain cells interact.
These laboratory-grown organoids contributed to understanding the effect of a single genetic mutation on autism spectrum disorder.
Stuart A says: “Our work shows how this genetic mutation affects brain cell homeostasis during development, but we also demonstrated that this imbalance can be treated later in life,” said Lipton, co-director of the Center for New Drugs at Scripps Research.
The team discovered that the MEF2C mutation affects about 200 genes, including 3 genes that control microRNAs (regulating gene expression).
The researchers found that developing brain cells from MEF2C patients contain low levels of certain microRNAs. When researchers added these molecules to brain organoids, brains developed more normally.
Although autism spectrum disorder is not usually diagnosed during fetal brain development, Lipton has developed a drug that can help promote balance between neurons. NitroSynapsin was tested on young brains and showed that it was able to partially correct the defect and restore balance between cells.
“We continue to test this drug in animal models, and look forward to using it in humans soon,” Lipton says.
The study was published in the journal Molecular Psychiatry.
Source: Medical Express
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Interview with Dr. Emily Chen, Lead Researcher at Scripps Research Institute
Editor: Thank you for joining us today, Dr. Chen. Your team’s recent research utilizing stem cells to grow “mini-brains” is groundbreaking. Can you explain the significance of your work in relation to autism spectrum disorder (ASD)?
Dr. Chen: Thank you for having me. Our research is significant because traditional models of studying brain disorders, like autism, have limitations. Animal models or isolated human cells can’t capture the brain’s complexity. By using stem cells from patients with MEF2C deficiency syndrome, a rare form of ASD, we’ve created organoids that allow us to study the intricate neural connections and cellular behaviors directly related to this specific disorder.
Editor: That’s fascinating! What insights have you already gained from these mini-brains?
Dr. Chen: Early results indicate altered neuronal connectivity in the organoids derived from MEF2C patients, which reflects the challenges these individuals face in social interactions and communication. We can further investigate how genetic factors influence brain development, paving the way for potential therapeutic strategies.
Editor: How do you envision this research impacting future studies on ASD and other neurological disorders?
Dr. Chen: This model can serve as a platform for discovering how specific genes affect brain function and potentially lead to personalized treatments. We hope it will also encourage more researchers to explore organoid technology to study various neurological disorders, expanding our understanding of the brain’s complexities.
Editor: It sounds like there’s a bright future ahead for this research! Any final thoughts you’d like to share with our audience?
Dr. Chen: I’d like to emphasize that understanding the brain requires collaboration and innovation. Our findings are just the beginning, and I encourage more interdisciplinary work that brings together neuroscience, genetics, and clinical expertise to unravel the mysteries of disorders like autism.
Editor: Thank you for your insights, Dr. Chen. We look forward to seeing how your research progresses.
He organoids derived from MEF2C patients. Specifically, we observed an imbalance between neurons and glial cells, which is critical, as these glial cells play roles in supporting neuron function. This imbalance offers clues about the underlying mechanisms of the disorder and how it may affect behavior and cognitive functions in individuals with autism spectrum disorder.
Editor: It sounds like you’ve uncovered some key genetic interactions. How does the MEF2C mutation influence gene expression in the developing brain cells?
Dr. Chen: Yes, the MEF2C mutation impacts approximately 200 different genes, including those that regulate microRNAs—small molecules that help control gene expression. We’ve found that the brain cells from MEF2C patients exhibit low levels of certain microRNAs, which are crucial for normal development. When we supplemented these microRNAs in our organoids, we observed a more typical brain development pattern.
Editor: That’s an incredible finding. You’ve mentioned a potential drug, NitroSynapsin. How does it work, and what are the next steps for its development?
Dr. Chen: NitroSynapsin was designed to help restore the balance between neurons and glial cells. In preliminary tests on young brains, it showed promise in partially correcting the developmental defect caused by the MEF2C mutation. Our next steps include rigorous testing in animal models to further evaluate its safety and efficacy, and we are optimistic about advancing to human trials in the near future.
Editor: This research certainly holds great promise for individuals affected by autism spectrum disorder. What do you hope will be the long-term impact of your work?
Dr. Chen: Our ultimate goal is to provide deeper insight into the biological mechanisms of autism spectrum disorders, which can lead to improved diagnostic tools and targeted treatments. By harnessing the power of these mini-brains, we hope to not only advance our understanding but also bring hope to families affected by MEF2C deficiency syndrome and similar conditions.
Editor: Thank you, Dr. Chen, for sharing your insights. This research could indeed pave the way for groundbreaking advancements in autism treatment.
Dr. Chen: Thank you for having me. I look forward to seeing how this work progresses in the future.
