Human Brain Organoids in the Preclinical Phase of Drug Development for Migraine
Abstract
Developing drugs for brain disorders poses significant hurdles. These challenges stem from the scarcity of optimal models for preclinical drug testing and the often observed lack of translation from preclinical to human clinical trials. Further complexity arises from the specific targeting required in many brain disorders, with drug delivery often impeded by the necessity to cross the blood-brain barrier (BBB). As such, the search for novel and efficient platforms for preclinical drug development is a vibrant area of research. In acknowledgment of the limitations of animal tests - such as the lack of translation owing to species differences - and in alignment with the principles of reduction, refinement, and replacement (3Rs), the scientific community is moving towards promoting animal-free drug development plans. In this context, human brain organoids are rapidly emerging as potential alternatives to traditional methods. These early-stage in vitro models, mirroring in vivo complexities, hold great promise for preclinical drug testing for brain disorders. Stable organoid phenotypes and the uncovering of disease-specific features could soon elevate them to a valuable strategy in pharmaceutical testing for a range of brain disorders. Recent advancements in assay-ready organoid platforms and microfluidic chips present considerable potential for the application of human brain organoids in drug development. This commentary briefly discusses the generation of human brain organoids…
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