A pioneering brain map could revolutionize treatment for Parkinson’s disease

Parkinson’s disease is the second most common neurodegenerative condition in Singapore, affecting about three in 1,000 people aged 50 years and above. This disorder harms dopaminergic neurons in the midbrain, which secrete dopamine to regulate movement and learning. Restoring these neurons can ultimately relieve symptoms such as tremors and difficulty moving.

To elucidate how dopaminergic neurons form in laboratory settings, the team created a two-step mapping approach called BrainSTEM (brain single-cell second-cell mapping). In collaboration with partners including the University of Sydney, they characterized nearly 680,000 cells from the fetal brain to map the full cellular landscape.

The second high-resolution projection targets the midbrain with additional precision and identifies dopaminergic neurons. This “comprehensive reference map” now serves as a global standard for assessing how accurately midbrain models match real human biology.

Dr Hilary Toh, an MD candidate from the Neuroscience and Behavioral Disorders Program at Duke University School of Medicine at the National University of Singapore and one of the first authors of this paper, said:

“Our data-driven blueprint helps scientists produce high-output midbrain dopaminergic neurons that faithfully reflect human biology. Grafts of this quality are pivotal to increasing the effectiveness of cell therapy and reducing side effects, paving the way for providing alternative treatments for people with Parkinson’s disease.”

Published in Advancement of scienceThe study suggests that many of the methods used to grow midbrain cells also generate unwanted cells originating from other areas of the brain. These results suggest that both experimental protocols and data analysis pipelines need to be improved to detect and remove these non-target populations.

Dr. Jun Ouyang, principal research scientist from the Duke-NUS Center for Computational Biology and one of the senior authors of the study, said:

“By mapping the brain at single-cell resolution, BrainSTEM gives us the precision to differentiate even minute, non-target cell populations. This rich cellular detail provides a critical foundation for AI-based models that will change how we group patients and design targeted treatments for neurodegenerative diseases.”

Assistant Professor Alfred Sun of Duke University’s Neuroscience and Behavioral Disorders Program, who is also a senior author on the paper, added:

“BrainSTEM represents an important step forward in brain modeling. By offering a rigorous, data-driven approach, it will accelerate the development of reliable cell therapies for Parkinson’s disease. We are setting a new standard to ensure that the next generation of Parkinson’s models truly reflects human biology.”

The researchers will release their brain atlases as open source references and provide the multilevel mapping approach as an out-of-the-box package. Because BrainSTEM can be applied to isolate any cell type in the brain, laboratories around the world can use it to deepen insight, streamline workflow, and accelerate discovery across neuroscience.

Professor Patrick Tan, Senior Vice Dean for Research at Duke University-NUS, said:

“This study redefines the standard—creating multi-level maps as essential to capturing cellular detail in complex biological systems. By revealing how the human midbrain develops in such detail, we will accelerate Parkinson’s research and cell therapy, deliver better care and offer hope to people with the disease.”

This work received support from programs including the USyd-NUS Ignition Grant and the Duke-NUS Parkinson’s Disease Research Fund through a generous donation from the Ida C. Morris Falk Foundation.

Duke-NUS remains a leader in medical research and education, and is committed to improving patient care through scientific innovation. This study advances ongoing efforts to understand basic brain mechanisms and develop new therapeutic strategies for neurological conditions.