Description
Despite extensive preclinical efforts, effective therapies for brain disorders remain scarce, largely due to the limited predictive power of existing experimental models. While many candidate compounds show robust efficacy in animal models, translation to human patients has been disappointing. This gap underscores the need for scalable, human-relevant platforms capable of recapitulating key aspects of brain circuit organization while remaining compatible with drug discovery pipelines.
Human induced pluripotent stem cells (hiPSCs) have opened new perspectives by providing access to the patient’s own genetic, molecular, and cellular context. However, their relevance in vitro is frequently limited by their use in isolated and artificial culture systems that fail to reproduce tissue-level organization and circuit-level interactions. By integrating hiPSC-derived cells with organ-on-chip technologies, human stem cells can instead be deployed within engineered microenvironments that better recapitulate physiological architecture and function, enabling drug testing in reconstructed patient-specific tissues.
Here we introduce brain-on-chip models that recapitulate both healthy and pathological conditions, including Huntington’s disease and neurodevelopmental disorders. These microfluidic platforms rely on compartmentalized architectures that enable controlled neuronal connectivity, long-term culture, and functional interrogation, while remaining compatible with standardized fabrication and scalable experimental workflows. We are now developing "humanized” versions of these platforms by incorporating patient-derived stem cells for these neuropathological conditions.
Using these next-generation human brain-on-chip devices, we evaluate the therapeutic potential of neuroprotective compounds that have already demonstrated promising efficacy in various animal-based models of Huntington's disease. This work thus aims to facilitate and accelerate the transfer of therapeutic candidates toward clinical trials by providing predictive, human-relevant, and engineering-driven preclinical platforms that complement existing animal models.