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