Parkinson's disease: How lab grown mini-brains could spur treatments

Upwards of 10 million people globally and nearly 1 million in the United States live with Parkinson’s disease, which has no approved treatments. The only option for patients is drugs that can keep the degenerative condition in check, rather than tackle its root causes.

A group of scientists now wants to upend that dynamic by leveraging lab-grown, human mini-brains to spur Parkinson’s research and drug development. In a study first published in the July edition of the journal Annals of Neurology, scientists used these synthetic mini-brains to mimic the activity of a regular human midbrain, which is critical to muscle movement and visual and auditory processing affected by Parkinson’s disease.

In essence the researchers replicated what an actual human brain would go through if it carried all the risk factors for a certain brain disease, in this case Parkinson’s. That’s particularly important since drug development for the disease must currently be done using mouse brains, which may produce different results than when using those of humans. For instance, certain biological wear and tear doesn’t manifest in a mouse, and a mouse model in Parkinson’s R&D may not produce the kinds of biological by-products linked with the disease.

“Re-creating models of Parkinson’s disease in animal models is hard, as these do not show the progressive and selective loss of neurons that produce the neurotransmitter dopamine, a major feature of Parkinson’s disease,” said Ng Huck Hui of the Agency for Science, Technology and Research’s Biomedical Research Council and the study’s senior coauthor.

The inability to directly access the brain and the complexity of the nervous system are key reasons brain drugs are so hard to create. To wit: The last Parkinson’s treatment approved by the Food and Drug Administration (FDA) was Kyowa Kirin’s Nourianz in 2019, and that was as a therapy added on to another one that controls symptoms rather than the disease.

The hope is that a better understanding of what a Parkinson’s disease patient’s brain goes through will make it easier to deconstruct the illness and spur drug development.

The researchers created the pea-size mini-brains by growing stem cells that create neurons. They were able to modify this human-based mini-brain with genetic tweaks to the stem cells that, in turn, mimicked the genomic qualities associated with a higher risk for Parkinson’s.

For this study, the researchers focused only on Parkinson’s, the second-most common neurodegenerative condition in the U.S. and second only to Alzheimer’s. But they hope that their synthetic, genetic template can be used in all manner of future brain disease research.

The study was conducted by researchers from the Agency of Science, Technology and Research’s Genome Institute of Singapore, Singapore’s National Neuroscience Institute, and Duke-NUS Medical School.