Mayo Clinic scientists develop mini brain models to study Lewy body dementia

Lewy body dementia (LBD) is a progressive neurodegenerative disease that shares features with both Parkinson’s disease and Alzheimer’s disease, but can be more difficult to diagnose. Symptoms may include hallucinations, movement disorders, cognitive problems, sleep problems and depression.

To better understand how the disease develops, Mayo Clinic scientists have created mini brain models in a dish that closely match key features of the brains of patients with Lewy body dementia. Minibrains, also called brain organoids, are laboratory-grown clusters of cells that mimic the human brain structure. The team also identified four potential drug compounds that could offer promising approaches to treating the disease. Their findings have been published in Science Advances.

There is no cure for LBD, and scientists say few accurate preclinical models are available to study it. A hallmark of the disease is a protein called alpha-synuclein, which is encoded by the SNCA gene. This protein is found in nerve cells of the brain and can build up into masses called Lewy bodies, which can contribute to the symptoms of dementia.

To better understand the pathology of the disease, a Mayo Clinic research team led by neuroscientist and senior author Na Zhao, M.D., Ph.D., developed preclinical mini-brain models using stem cells from LBD patients that produce extra copies of the had the SNCA gene. , which may have caused their condition. The patients donated their skin cells at diagnosis while they were still alive. Scientists then converted the skin cells into stem cells and used them for research.

Using advanced genomic techniques such as single-cell RNA sequencing, which examines genetic material in individual cells, the researchers showed that their mini brain models mirrored the changes seen in the human brains of LBD patients who had their brains had donated to the Mayo Clinic Brain Bank. , making the models valuable tools for studying how the disease develops.

The researchers used their new model system to screen nearly 1,300 Food and Drug Administration-approved drugs, identifying four candidates that could help prevent the buildup of alpha-synuclein in neurons.

This study suggests that these mini brain models can effectively mimic disease development, providing a potential platform for testing individualized treatments for patients. The four identified drug candidates, which have the potential to inhibit alpha-synuclein and restore energy production in neurons derived from LBD patients, could be further refined or adapted to develop new treatments for LBD and associated dementias in the future .”

Na Zhao, M.D., Ph.D., senior author

Researchers say additional studies could introduce additional cell types to better mimic the complexity of the human brain. Researchers could then use these improved models to further investigate disease mechanisms, such as examining how risky genes influence the development of LBD.