A research team from the NIH National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories (MT, USA) has developed what they anticipate is the first cerebral organoid system for studying sporadic Creutzfeldt–Jakob disease (CJD). This could be a promising means of assessing and developing potential CJD treatments in the future.
Organoids have been utilized to study diseases such as Zika and Alzheimer’s disease, however, this is the first cerebral organoid system for studying CJD. This model will hopefully enable investigators to evaluate potential therapeutics for CJD and provide greater detail about human prion disease subtypes than currently used models, such as rodents and nonhuman primates.
In this study, published in Acta Neuropathologica Communications, researchers infected 5-month-old cerebral organoids with prions from two CJD subtypes, known as MV1 and MV2. After approximately 1 month, the infection was confirmed. The researchers then monitored the organoids for possible changes in health indicators, such as metabolism, for over 6 months.
The team observed that by the end of the study, all organoids that had been exposed to the samples of CJD displayed signs of seeding activity, indicating the presence of prion propagation. Organoids infected with the MV2 sample displayed greater seeding activity than organoids exposed to the MV1 sample. However, the MV1-infected organoids exhibited more damage than the MV2-infected organoids. The researchers also observed other disparities between the development of the MV1 and MV2 infections.
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The researchers recognized that cerebral organoids have certain limitations. Within the study, the authors stated that: “They are highly heterogenous, not vascularized and they may lack non-neuronally derived cells of the brain such as epithelial cells and microglia. Despite these limitations, these cultures represent the closest in vitro cell model to human brain currently available and offer the first human three-dimensional model of prion disease.”
Future investigation into the differences between the MV1 and MV2 infections may allow the researchers to further understand how different subtypes of CJD work. The researchers anticipate that eventually, the utilization of cerebral organoids may allow them to understand how to prevent cell damage in prion infections.
Sources: Groveman BR, Foliaki ST, Orru CD et al. Sporadic Creutzfeldt-Jakob disease prion infection of human cerebral organoids. Acta Neuropathol. Commun. 7(1), 12 doi:10.1186/s40478-019-0742-2 (2019); www.niaid.nih.gov/news-events/niaid-scientists-develop-%E2%80%9Cmini-brain%E2%80%9D-model-human-prion-disease