Scientists create "mini-brain" to study sporadic Creutzfeldt-Jakob disease

Scientists from the National Institutes of Health have used human skin cells to create what they believe to be the first brain organoid system, or "mini-brain," intended for the study of sporadic disease of Creutzfeldt-Jakob (CJD). CJD is a fatal neurodegenerative brain disorder in humans, which could be caused by an infectious prion protein. It affects about 1 million people. Researchers at the NIH's National Institute of Allergy and Infectious Diseases (NIAID) hope that the human organoid model will allow them to evaluate potential treatments for CJD and to provide more detailed information about the subtleties. types of human prion diseases than currently used rodent and non-human primate models.

Human brain organoids are small balls of human brain cells that range in size from poppy seed to pea. Their organization, structure and electrical signaling are similar to those of brain tissue. Since these brain organoids can survive for months in a controlled environment, diseases of the nervous system can be studied over time. The brain organoids have been used as models to study infection with Zika virus, Alzheimer's disease and Down's syndrome.

In a new study published in Acta Neuropathologica Communications, scientists at NIAID's Rocky Mountain Laboratories discovered how to infect five-month-old brain organoids with prions using samples from two deceased patients of two different CJD subtypes, MV1 and MV2. It took about a month to confirm the infection, and scientists monitored for more than six months changes in health indicators, such as metabolism, in organoids. At the end of the study, scientists observed that seeding activity, an indication of the infectious spread of prions, was present in all organoids exposed to CJD samples. However, seeding was more important in organoids infected with the MV2 sample than in the MV1 sample. They also reported that MV1-infected organoids were more damaging than MV2-infected organoids.

Scientists have also noted other differences between the evolution of MV1 and MV2 infections in organelles. They plan to further investigate these differences in the hope of identifying how different subtypes of CJD affect brain cells. In the end, they hope to learn how to prevent cell damage and restore the function of cells damaged by prion infection. The new system also offers the opportunity to test potential treatments for CJD in a tissue model that mimics the human brain.

Source:

NIH / National Institute of Allergy and Infectious Diseases

Journal reference:

Groveman, B.R. et al. (2019) Sporadic Creutzfeldt-Jakob Disease prion infection of human brain organoids. Acta Neuropathologica Communications. doi.org/10.1186/s40478-019-0742-2.