Using a novel model of antidepressant efficacy to discover new compounds and personalized treatments.

The World Health Organization estimates that bymajor depressive disorderMDDwill be the most common cause of disabilityworldwideAlthough approximatelyinAmericans will suffer from MDD during their lifetimemany patients with MDD go undiagnosed in primary care settingsandare incorrectly diagnosed with MDDGiven the substantial medicaleconomic and social costs involved with MDDthere is tremendous need for a simple objective biomarker test to aid clinicians in accurately identifying MDDNo test currently exists that can accurately diagnose MDD and distinguish it from other psychiatric conditionsFurtherclinical response to antidepressant therapy requires as much as two monthsThere is enormous need for a test that can predict response within a few days of the inception of treatmentThe potential market for an accurate diagnostic test for MDD is estimated at $B annuallyPayers of medical services would cover the cost of such a diagnostic test because accurately identifying and treating MDD would reduce the high medical costs arising from medical service delivery to patients with untreated depressionas well as improving outcomes for patients with comorbid medical conditions such as diabetes or heart diseaseAnother market for an MDD diagnostic test is pharmaceutical companiesThese companies have uniformly retreated from discovery efforts in mood disordersin part due to largescale failure of numerous clinical trialsPart of the reason for these failures is the enrollment of inappropriate patientsAn objective test of MDD could address this concern by providing certainty about the appropriateness of recruited subjectsThe Pax Neuroscience diagnostic biomarker G s Sequestration AssayGSAindicates that MDD patients have a significantly greater proportion of G s captured in lipid rafts compared to non depressed controls and can accurately identify patients suffering from MDDPax used the same principles that underpin the GSA to develop a CgliomaG sGFPFRAP assay which can reliably predict antidepressant efficacyThe proposed studies will convert that assay into high content screeningHCSformatenabling an HCS campaign to find novel small molecules that target MDDIn addition we will develop a secondary screen using Neural Stem Cellsi n d u c e d from f i b r o b l a s t s o f d e p r e s s e d subjects with known responses to antidepressantsSSRIsto confirm the efficacy of the screenThis secondary screen can be modified to evaluate treatment efficacy in MDD patientsThis is an exciting proposal that offers an underlying technology that can both find new drugs and develop personalized therapy for depression