Neurodegenerative target discovery platform

Inventors

Cirit, Murat • Alaybeyoglu, Begum • Sherfey, Jason Samuel • Rumsey, John Wayne • Shin, Yoojin

Assignees

Javelin Biotech Inc

Abstract

A microphysiological system (MPS) includes at least one first inlet for receiving a fluid medium. The MPS includes a brain module comprising brain tissue. The MPS includes a blood-brain-barrier (BBB) module comprising BBB tissue, the BBB module configured to receive the fluid medium. The MPS includes a crosstalk channel between the brain module and the BBB module, the crosstalk channel configured to promote a bidirectional crosstalk between the brain tissue and the BBB tissue in response to receiving the fluid medium at the BBB module. The MPS is configured for treating the brain tissue and the BBB tissue with a drug or a combination of drugs to determine a phenotypic effect and a transcriptomic effect of the drug. A drug perturbation is related to the phenotypic effect and the transcriptomic effect based on kinetic optimization.

Core Innovation

The invention provides a neurodegenerative preclinical drug discovery platform implemented as a microphysiological system (MPS). The platform includes a brain module comprising brain tissue and a blood-brain-barrier (BBB) module comprising BBB tissue, where the BBB module receives a fluid medium. The brain module and the BBB module are connected by a crosstalk channel configured to promote bidirectional crosstalk between the brain tissue and the BBB tissue in response to receiving the fluid medium at the BBB module.

The bidirectional crosstalk in the crosstalk channel is configured for exchange of one or more of nutrients, signaling molecules, and drugs between the brain module and the BBB module. The platform is configured to perturb tissues with drug(s) and measure phenotypic effects and transcriptomic effects. The platform determines kinetic drug-perturbation relationships to support target discovery and clinical trial translation.

The described platform further integrates neurovascular unit (NVU) architectures and sensing and measurement modalities, including integrated microelectrode array (MEA) electrophysiology and biomarker sensing with omics data generation. Computational pipelines are described for therapeutic target identification and ranking, including machine learning classifiers, context-specific genome-scale metabolic models, and quantitative systems pharmacology for in vitro to in vivo translation. The platform is described for neurodegenerative indications, including Parkinson’s disease, and for readouts linked to dopaminergic neuron-related pathology and neuroinflammation/oxidative stress biomarkers.

Claims Coverage

The document includes one independent claim directed to an MPS architecture with a brain module, a BBB module, and a crosstalk channel that supports bidirectional exchange. Dependent claims refine tissue/cell composition and add specific sensing/measurement and channel configurations, and relate the system to neurodegenerative disease contexts and specific crosstalk behaviors.

Overall claim coverage centers on an MPS with a brain module and a BBB module coupled by a crosstalk channel that drives bidirectional exchange of nutrients, signaling molecules, and drugs when fluid medium is introduced to the BBB module. Dependent claims further specify BBB channel arrangements, measurement/sensing features, and disease-relevant context for neurodegenerative disease modeling.

Stated Advantages

Documented Applications