PAIN THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase I: NIA

Description

Project Summary Abstract PTIis a novel small molecule AD therapeutic candidate with a novel target and mechanism of actionPTIbinds and reverses an altered conformation of the scaffolding protein filamin AFLNAto prevent Aandapos s tight binding to and toxic signaling via thenicotinic acetylcholine receptornAChRas well as Aandapos s aberrant activation of toll like receptorTLRHenceby restoring FLNAandapos s native shape and blocking these two toxic cascadesPTIreduces both tau hyperphosphorylation and neuroinflammationDownstream effects include reduced neurofibrillary lesions and amyloid depositssuggesting disease modificationand improved synaptic plasticity and function ofnAChRNMDAR and insulin receptorssuggesting symptomatic improvementWe will initially pursue a label claim of symptomatic improvement instead of the more difficult claim of disease modification and will therefore conduct clinical studies in mild to moderate ADConducted under a US INDthe first in human clinical trial showed no drug related adverse effectsAEsand dose proportional pharmacokineticsPKof the oral solutionIn this administrative supplement proposalwe include additional development costs for PTImostly related to the upcoming multidose clinical trial Project Narrative PTIis a novel compound has been shown to alleviate multiple pathological features of AD in mouse models and in postmortem AD brain tissueincluding receptor dysfunctionsinflammationimpaired synaptic plasticityand the hallmark plaques and tanglesThese multiple therapeutic benefits suggest PTImay improve cognitive function as well as slow the course of the diseaseWe additional costs in this administrative supplement that are mostly related to the upcoming multidose clinical trial and not included in other grant proposals