Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

Abstract

Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways to treat disease. Organoids of the liver, kidney, intestine, lung, and brain have been developed in recent years. Human brain organoids are used for understanding pathogenesis and investigating therapeutic options for neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders. Theoretically, several brain disorders can be modeled with the aid of human brain organoids, and hence the potential exists for understanding migraine pathogenesis and its treatment with the aid of brain organoids. Migraine is considered a brain disorder with neurological and non-neurological abnormalities and symptoms. Both genetic and environmental factors play essential roles in migraine pathogenesis and its clinical manifestations. Several types of migraines are classified, for example, migraines with and without aura, and human brain organoids can be developed from patients with these types of migraines to study genetic factors (e.g., channelopathy in calcium channels) and environmental stressors (e.g., chemical and mechanical). In these models, drug candidates for therapeutic purposes can also be tested. Here, the potential and limitations of human brain organoids for studying migraine pathogenesis and its treatment are communicated to generate motivation and stimulate curiosity for further research. This must, however, be considered alongside the complexity of the concept of brain organoids and the neuroethical aspects of the topic. Interested researchers are invited to join the network for protocol development and testing the hypothesis presented here.

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

“…Brain organoids are three-dimensional models that mimic the structure and function of the human brain. They can be used to investigate altered neuronal pathways, protein expression, and metabolic pathways associated with migraines [241][242][243][244]. This approach offers a unique opportunity to study the disease in a more physiologically relevant system.…”

From CGRP to PACAP: Unraveling the Next Chapter in Migraine Treatment

“…The use of human brain organoids in migraine research is an emerging area of study [209]. Brain organoids are three-dimensional models that mimic the structure and function of the human brain [213]. They can be used to investigate altered neuronal pathways, protein expression, and metabolic pathways associated with migraines [214][215].…”