Skip Ribbon Commands
Skip to main content

Lab-grown mini-brains spark hope for PD research

How do you study a disease when you have little or no access to it? This challenge is a key reason why there is currently no cure for Parkinson’s Disease (PD). Now a team from the National Neuroscience Institute (NNI) has helped to develop a groundbreaking solution: growing mini versions of the mid-brain outside the body! Dr Alfred Sun, Associate Research Scientist, NNI, shares more about this discovery and how it will help find a cure for PD, particularly in Asians.

What sparked this research? 
I’m particularly interested in studying the brain because it is such a complex organ - one small change can drastically affect your independence and personality. For example, in the case of PD, it is caused by the breakdown of dopamine-producing cells in the mid-brain. Dopamine is a neurotransmitter – a chemical released by nerve cells (neurons) to send signals to other nerve cells. It plays a vital role in planning and controlling movement which is why people with PD often suffer from tremors and movement difficulties. 

Therefore, discovering ways to prevent the destruction of these dopamine-producing cells and helping them to regenerate is key to finding a cure for PD. It’s impossible to study and conduct tests on these cells in a living person without causing harm. Until now, researchers have had to use cultures of two-dimensional (2D) layers of these cells in the laboratory. Unfortunately, potential cures that work on these 2D layers in the laboratory often fail during early drug trials. The reasons are multiple, and one of them is that brain cells are team players - they cluster around and communicate with each other and always function as part of a larger network in 3D. 

It was critical that we find a way to replicate these cells in conditions that closely mirror the brain. This will help us tremendously in understanding the important structural relationship between these cells and safely test potential new treatments on living human cells. 

How did you create these mini mid-brains?
We were inspired by research that was published in 2013 by German scientists who managed to grow mini whole brains (organoids). For PD, the critical area is the mid-brain where the dopamine-producing cells are found. 

It took our team of 12 - researchers from NNI, Genome Institute of Singapore and Duke-NUS Medical School - about two years to succeed. Stem cells were used to start the cultures and we supervised them closely to monitor their progress. Every day for two years, at least one of us would be in the laboratory, babysitting the cultures and measuring the growth and development of the cells. 

The dopamine-producing cells in the mid-brain contain a dark pigment so we knew that the mini brains would need to be black to be successful. When they started to develop, it was a bit disappointing to see they were pink but we carried on monitoring them every day to see what would happen. 

After more than three months, we suddenly noticed black dots on some of the cells. Our initial reaction was panic because we thought they had been contaminated by mould, but when we studied the cells under the microscope, we realised the black was caused by the dark pigment. It was a moment of celebration and huge relief! We checked the cells’ ultra-structures and did multiple assays to replicate our findings to ensure they were robust. 

What do these mini brains look like?
When they start growing and first become visible to the naked eye, they look like tiny pink balls. It takes about four months for them to grow to balls about the size of a pencil eraser. At this point they are fully grown and you can see the tiny black cells with the naked eye. 

What’s next for you and your research team?
The mutations that are associated with PD in Caucasians do not completely overlap with those that affect Asians. So now we are creating mini brains with the Asian genetic PD variant to study the impact this has on the cells as they grow. This will help us develop better treatments for Singaporeans and Asians with PD and provide patients with more targeted, personalised medicine. We also need to speed up the growth and development of the mini-brains so they can be used more effectively for drug development to find better treatments and hopefully a cure for this debilitating disease.