To help us crack the complex puzzle that is our own brains, scientists have been growing miniature versions in the lab. Now, a team in Singapore has made a major breakthrough by growing mini-brains with the pathological features of Parkinson’s disease for the first time, potentially paving the way towards better treatments.
Much of the prior research into Parkinson’s has been conducted in mouse models of the disease, but that’s far from a perfect analog of humans. Some of the most characteristic pathological features of Parkinson’s don’t actually appear in mice, leading to an incomplete picture of disease progression or experimental treatments.
“Recreating 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,” says Professor Ng Huck Hui, senior co-author of the study. “Another limitation is that experimental mouse models of Parkinson’s disease do not develop characteristic clumps of proteins called Lewy bodies, which are often seen in the brain cells of people with Parkinson’s disease and a type of progressive dementia known as Lewy body dementia.”
In recent years, scientists have developed more accurate models known as brain organoids. These pea-sized lumps of brain tissue are grown from human stem cells in a medium that closely resembles that in which the brain normally develops, coaxing the cells to form a 3D cluster of neurons and other cells that resembles the actual brain, in miniature. Scientists have used these brain organoids to study development, disease and drugs, and even managed to make some that sprouted blood vessels and working eye-like structures.
To create brain organoids that exhibited signs of Parkinson’s, the researchers engineered the DNA of stem cells to give them the genetic risk factors associated with the disease. And sure enough, the resulting mini-brains showed signs of progressive loss of their dopamine-producing neurons, as well as Lewy bodies.
“These experiments are the first to recreate the distinctive features of Parkinson’s disease that we see only in human patients,” says Hyunsoo Shawn Je, senior co-author of the study. “We have created a new model of the pathology involved, which will allow us to track how the disease develops and how it might be slowed down or stopped.”
The team has already started to us the mini-brains to study how these Lewy bodies form, and test drugs that might be able to halt progression of the disease.
The research was published in the journal Annals of Neurology.
