Scientists in Singapore have made a big leap on the study of the human brain by growing 'mini-brains' for research.

Measuring about 2mm to 3mm long, these mini versions of the human midbrain are hoped to be able to help researchers develop treatments and conduct other studies into Parkinson's Disease (PD) and other ageing-related brain diseases.

While other researchers in the world have successfully grown other parts of the brain, the local team are the first to grow the midbrain tissue.

The key player: Neuromelanin

The mini midbrains are three-dimensional miniature tissues, grown from stem cells in the laboratory and contain properties of specific parts of the human brains. The brain organoids are the first to contain the necessary hallmarks of the human midbrain, which are dopaminergic neurons and a black pigment, neuromelanin.

Neuromelanin has been associated with protecting cells from dying, and is diminished in brains of patients with Parkinson's disease. The reduction in neuromelanin production leads to the degenerative condition of PD patients, which includes tremors and impaired motor skills.

The human midbrain can also be known as the information superhighway. It mainly controls auditory, eye movements, vision and body movements and contains special dopaminergic neurons that produce dopamine - which carries out significant roles in executive functions, motor control, motivation, reinforcement, and reward.
High levels of dopamine elevate motor activity and impulsive behaviour, whereas low levels of dopamine lead to slowed reactions and disorders like PD, which is characterised by stiffness and difficulties in initiating movements.

"A game-changer for drug development"

Midbrain organoids, measuring about 3 mm across, cultured in the laboratory dish. Note the black pigments are neuromelanin. Copyright: A*STAR's Genome Institute of Singapore

Midbrain organoids, measuring about 3 mm across, cultured in the laboratory dish. Note the black pigments are neuromelanin. Copyright: A*STAR's Genome Institute of Singapore

Prior to this discovery, researchers studying Parkinson's often relied on simulations or studies on animals. Studies on the mini-brains can be conducted in the laboratory on cells that mimic the functions of the section of the brain that is affected by the disease.

Assistant Professor Shawn Je from Duke-NUS Medical School's Neuroscience & Behavioural Disorders Programme said, "It is remarkable that our midbrain organoids mimic human mid brain development."

"The cells divide, cluster together in layers and become electrically and chemically active in three-dimensional environments like our brain," he added, "Now we can really test how these mini-brains react to existing or newly developed drugs before treating patients - which will be a game changer for drug development."

Parkinson's is a gradually progressive neuro-degenerative disorder which affects a person's control of movement, including speech. According to the Health Ministry, three in every 1,000 Singaporeans aged over 50 are afflicted by the disease. It also affects an estimated seven to 10 million people worldwide and there are others who are affected by other causes of parkinsonism.

The research is jointly led by Professor Ng Huck Hui from A*STAR'S Genome Institute of Singapore (GIS) and Assistant Professor Shawn Je from Duke-NUS Medical School. It is a collaborative research between GIS, Duke-NUS, and the National Neuroscience Institute (NNI) is funded by the National Medical Research Council's Translational Clinical Research (TCR) Programme In Parkinson's disease (PD) and A*STAR. Other collaborators are from the Lieber Institute for Brain Development, the Johns Hopkins University School of Medicine, and the Nanyang Technological University. MIMS