Direct Conversion of Human Fibroblasts into Neuronal Cells by Small Molecules (hCiN)

Licit and illicit drug use places a large burden on the nationandapos s health care systems and the economycosting more than $billion annuallyAddiction is a chronic brain disease that leads to a compulsive desire for drugs despite significantly harmful consequencesincluding direct effects on health as well as detriments to societyincluding disintegration of familieschild abuseloss of employmentand a broad array of crimesReprogramming of human somatic cells to alter cellular identity has enormous potential for neurological disease modelinghigh throughput drug screeningcell therapyand personalized medicineHoweverseveral challenges remain before patient specific cells produced by reprogramming can provide reliable insights into neurological disease mechanismse gDrug abuseaddictionother neurological disordersor be efficiently applied to drug discovery and transplantation therapyUsing our innovative patented technology to develop ArtificialD Microenvironment Niche and screen for reprogramming small moleculesUS Patentwe have developed a preliminary small molecule cocktail that efficientlyup toof starting cell numbersmostly Glutamatergic Neuronsand directly converts human fibroblasts into neuronsbypassing the neural progenitor stageChemically induced NeuronshCiNIn this Phase I proposalwe attempt to demonstrate the feasibility of this methodology by optimizing our preliminary hCiN cocktails while investigating hCiN functionally with molecularcellularelectrophysiological assays and in a mouse brain transplantation model Licit and illicit drug use places a large burden on the nationandapos s health care systems and the economycosting more than $billion annuallyAddiction is a chronic brain disease that leads to a compulsive desire for drugs despite significantly harmful consequencesincluding direct effects on health as well as detriments to societyincluding disintegration of familieschild abuseloss of employmentand a broad array of crimesStudies outlined in this proposal attempt to demonstrate feasibility of a methodology that provides for robust reprogramming of patient specific neurons from fibroblast cells making possible elucidation of reliable insights into neurological disease mechanismse gDrug AbuseAddiction and other neurological disordersfor applications to preventiondrug discovery and transplantation therapy