Rapid Production of Regional and Disease Specific Human Astrocytes for CNS Drug Discovery

Project Summary AbstractThe personalsocietaland economic burden that disorders of the central nervous systemCNSplace on the United States is tremendousFromthe FDA approved justnew drugs to treat CNS disorders covering the clinical areas of neurologypsychiatryand painThat averages to just three new chemical entitiesNEIsper yearwhile clinical trial failure rates for CNS drug development remain greater thanAlthough the reasons for this exceedingly high level of attrition are myriad and complexthe central challenge to drug development is that platforms for early preclinical identification and validation of novel compounds are often not relevant to the disease target cells and phenotypesBrainXellIncseeks to address these issues head on by generating in vitro model systems with human neurons and astrocytes that more closely approximate the human CNSFunctional loss or impairment of astrocytes is implicated in a wide range of pathological processes and neural disordersincluding Alzheimerandapos s diseaseParkinsonandapos s diseaseamyotrophic lateral sclerosisALSand epilepsyThis SBIR Phase I proposal is to produce large quantities of highly enrichedregional specific astrocytes in a rapid and consistent manner that meet high throughput screeningHTSrequirementsRecentlywe have developed a novel method for rapid generation of enriched and functional spinal astrocytes from iPSCs inweeks by applying inducible expression of gliogenic transcription factors NFIA and SOXIn this studywe will apply the same strategy to generate other regional specific astrocytessuch as corticalmidbrainand hindbrain astrocytes as well as ALS disease astrocytesWe will then validate whether these astrocytes produced in vitro can exhibit similar gene expression and function as their in vivo and disease counterpartsThe success of this study will not only enable us to expand our astrocyte product linebut also provide a service to manufacture astrocytes from patient iPSCs for drug discovery Project NarrativeBrainXell will develop technology to produce a specialized support cell in the human brain called an astrocyteStarting with adult stem cellsdifferent types of astrocytes corresponding to various regions of the brain will be producedand they will also be made from stem cells from individuals with certain diseasesThese cells will be commercialized as a high quality product to allow pharmaceutical companiescustomersto use them to discover new drugs for the treatment of neurologic diseases such as ALSParkinsonandapos sand Alzheimerandapos s