The ANA Q&A: Jack Parent, MD, FANA and Sally Temple, PhD | Brain Organoids

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Brain Organoids: Advancing precision medicine and neuroscience

The opening symposium of the ANA’s 2022 Annual Meeting, “Brain Organoid Modeling of Neurological Disorders,” takes place Saturday, October 22, from 5:45 to 7:15 p.m. Register now to attend the Annual Meeting in Chicago!

A groundbreaking new tool in neuroscience research, brain organoids are the focus of the ANA2022 opening symposium. These human-stem-cell-derived brain tissues grown in 3-D culture are yielding insight into a host of neurological diseases and neuroscience questions. 

We talked to symposium chairs Jack Parent, MD, FANA, William J. Herdman Professor of Neurology at the University of Michigan Medical School; and Sally Temple, PhD, Scientific Director of the Neural Stem Cell Institute in Rensselaer, NY, to hear why this topic is so important.

Why are brain organoids such an exciting development?

Parent: Brain organoid cultures allow us to model human disease with 3-D human brain-like tissue. Using them has already yielded interesting findings for neurodevelopmental disorders, genetic epilepsies, and neurodegenerative and infectious diseases. A lot of neurological diseases are network diseases that will be easier to study in a 3-D system. 

Temple: There is a huge advantage in the fact that we’re looking at human cells—and we can grow human cells from patients. That is incredibly powerful.

With these 3-D organoids, the cells can interact in a way that is more representative of the in vivo environment. We’re starting to be able to incorporate other cell types such as vascular cells to reconstruct more of that complex brain environment. And you can culture organoids for long periods; you can keep them going literally for years.

What are some surprising early findings?

Temple: We’re asking, can we use these little balls of cells, grown from patients’ stem cell lines and developed for a few months in culture, to model diseases that may not manifest for decades? The exciting thing is, we can see signs of neurodegenerative disease in organoids that are only a few months old. 

Parent: Brain organoids can also be used to study infectious disease and actually look at evolutionary changes, comparing organoids from non-human primates and humans, which is exciting. We’ll also talk about a new approach that is going to be really powerful: patterning different brain regions and fusing them to make what’s called assembloids.

Temple: It’s like the Lego brain. You can make different modules and then stick them together to recreate connections between brain regions.

Where is the field going next?

Parent: Having a human-brain-specific model to test precision therapies will help translation of new treatments. We often go from successful mouse drug trials to human trials that are unsuccessful. Brain organoids are an intermediate step that maybe could get us better precision therapies.

Temple: Organoids reflect the complexity of the human brain to an extent, and we can make thousands. They’re valuable for discovery but also for testing candidate drugs in a 3-D system that is made of human cells instead of mouse or rat cells. We’ll always need in vivo models for safety testing, but there are opportunities with organoid systems for efficacy testing.

Parent: These are still early days in the field and it’s really advancing rapidly. There’s going to be more exciting improvements in organoids in the not-too-distant future.

Want to learn about more of the groundbreaking research being conducted by ANA members? Read past editions of The ANA Q&A.