Connecting blood vessels to mini-brains
The overall aim of the CONNECT consortium is to create a human induced pluripotent stem cell (iPSC)-derived model that connects an artificial blood vessel with a functional blood-brain barrier (BBB) to cerebral organoids to predict the efficacy of existing and newly-developed compounds to enter and affect the brain. The consortium is a newly established public private partnership.
The development of such a BBB model is highly relevant as an effective therapy for neurological disorders is still lacking. Additionally, current animal and cell models of the BBB are not always predictive or specific enough for the human situation. Today, it remains a challenge to effectively treat patients suffering from a brain disorder. The Blood-Brain Barrier (BBB), which protects the brain from unwanted compounds also hampers the delivery of therapeutics into the brain. Moreover, available animal models do not fully reflect disease conditions as seen in patients, making drug discovery a challenge and creating a need for models that predict all aspects of the route and effects of a drug upon administration. These disorders include Alzheimer's disease, multiple sclerosis, and stroke, and account for 7.1% of the total global burden of disease. Total yearly costs of all brain disorders in Europe adds up to at nearly €800 billion and in the Netherlands alone to €30 billion, emphasising that these conditions pose a large societal and health care challenge.
This project will differentiate human pluripotent stem cells into a functional BBB and connect it with mini-brains to take the first steps towards model development. This is a unique approach, as they are the first to build such a complex 3D-model to mimic all aspects of the human brain to enable testing and selection of effective compounds for currently incurable neurological diseases. This innovative approach leads to a human measurement model that is more predictive for the situation in patients than the current animal and 2D cell models.
This novel human measurement model can form the basis of novel compound discovery programs to select drugs and nutrients that will be effective in patients. Besides, this unique platform is ideal to conduct future fundamental studies to uncover pathological mechanisms using patient-derived models.
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