Bioartificial Brain Slices for Drug Screening

Abstract Summary ISurTec is seeking SBIR funding to continue the development of a versatile bioartificial brain slice scaffolddesigned for use in electrophysiological drug screening assaysAcute brain slicesprepared from rats or miceare currently the `gold standardandapospreparation for characterizing neural tissue responses to drugstoxinsor other agentsHoweverthe limited number of brain slices produced per animalcoupled with the high costs of animal care and useremains a major limitation of this approachFurthermoredue to interspecies genetic variationpreclinical data acquired through the use of acute brain slices will usually be of limited predictive power for human clinical trials and postmarket surveillanceThe Phase I project demonstrated thatD scaffolds containing an open field architectureblueprintcan spontaneously induce hippocampal CACAlike neural circuits from dissociated hippocampal cellsThese bioartificial brain slices reliably generate field excitatory postsynaptic potentialsfEPSPsthat are sensitive to glutamate receptor antagonistsPhase I was accomplished through simultaneous control over the nanotopography and surface chemistry using ISurTecandapos s photoreactive nanofibersIn Phase IIwe will modify the scaffold design to improve both its performance and its manufacturability as well as develop and optimize protocols for culturing GlutamatergicGABAergicand Dopaminergic hNPCs on the scaffolds in conjunction with hGPCsThe optimized protocols will be used for assay validationand the bioartificial human brain slices will be field tested for both drug development and toxicologyThe human bioartificial brain slice is expected to be a valuable tool for drug development concerning a wide variety of human neurological diseases and disordersincluding addictionADD ADHDdepressionParkinsonandapos s diseasepain processingand schizophreniaOur technology will advance the field of Central Nervous SystemCNSDrug Development by overcoming the following two limitations of acute slices derived from rodentsits limited human relevance andits high burden and cost of animal care compliance and oversightRelevant to the current brain slice techniqueour technique is low cost and decreases animal sacrifice while increasing the predictive power of human neural progenitor cell assaysThis SBIR project will create a bioartificial brain slice scaffold for patterningdimensionalhighly laminar open field arrays of human neuronal co cultures for electrophysiology Project Narrative The use of acute brain slicesthin sections of living brain tissue harvested from rats or miceis the most accessible and physiologically relevant drug screening assay available to approximate systems level effects on the central nervous systemCNSand spinal cordHoweverthis approach suffers from high costs due to animal careuseand oversight as well as limited clinical relevancenonhuman tissueThis SBIR project will create a bioartificial brain slice scaffold for patterningdimensionalhighly laminar open field arrays of human neuronal cocultures for electrophysiology