Scientists from different agencies and research facilities have turned to laboratory manufactured human mini-brains to study the onset and progression of Parkinson’s disease.
Studies into how the brain works are taking a huge leap after Singaporean scientists found a way to grow miniature brains that can mimic the pathological features of certain diseases.
Scientists from the Agency of Science, Technology and Research‘s Genome Institute of Singapore, the National Neuroscience Institute and Duke-NUS Medical School have turned to laboratory manufactured human mini-brains to study the onset and progression of Parkinson’s disease. Aptly called “human midbrain-link organoids,” the three-dimensional, multicellular, in vitro tissue construct mimics the human midbrain, enabling researchers to evaluate the pathological features of different illnesses. For this particular study, they concentrated on Parkinson’s.
The organoids are pea-sized and are grown human stem cells to form a bundle of neurons and other cells that are found in the human brain. By manipulating the DNA of the starting stem cells to match certain genetic risk factors in patients who had been diagnosed with Parkinson’s, the researchers managed to build neuron-equipped organoids that can demonstrate how Lewy bodies work and show the progressive loss of neurons that contain dopamine, which is at its lowest levels in diseases like Parkinson’s and Alzheimer’s.
“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. 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,” said Professor Ng Huck Hui, the senior group leader at GIS A*STAR and senior co-author of the study.
This experiment marks a major milestone in the field of brain science, especially as previous researchers had mainly relied on results from studies on mouse brains. By mimicking the human brain, the scientists are able to more accurately recreate Parkinson’s distinct features that are only seen in humans. This could open up further research into other neurodegenerative diseases in the future, and no longer limits studies to current animal models.
“It’s a major challenge to extend healthy living years in an aging global population, whose physical and cognitive performance often declines due to neurodegenerative disorders. This discovery provides insights and a ‘humanized’ disease model that can facilitate drug testing against Parkinson’s disease and dementia. Our organoid model with a genetic mutation on the GBA gene is also highly relevant as we have several of these genetic mutation carriers locally,” added Professor Tan Eng King, deputy medical director for academic affairs at NNI and the study’s other senior co-author.
The scientists are already using organoids to find out why and how Lewy bodies are created in human brain cells. They are also looking at screening drugs that have the potential to stop the progression of brain diseases.
Parkinson’s disease is an age-related neurodegenerative disorder that affects three in 1,000 Singaporeans aged 50 years and above. In the U.S., around 60,000 are diagnosed with the disease every year. On a global scale, Parkinson’s is listed as the fastest growing disorder with over 10 million affected.
The study is published in the Annals of Neurology.
