Novel formulations of Allopregnanolone to treat Alzheimer's Disease

PROJECT SUMMARY ABSTRACT Alzheimer s diseaseADis a progressive multifactorial disease affecting more thanmillion people worldwide and is the most common dementia of late lifeTo dateno interventions have demonstrated substantial therapeutic efficacy to preventdelay or treat ADCurrent thinking in the field embraces the complexity of AD pathophysiologywhich has enabled a more diverse therapeutic pipeline targeting multiple aspects of the diseaseThe neurosteroid allopregnanoloneAllois under development as a regenerative therapeutic to regenerate the degenerated Alzheimer s brainAllo is an innovativeregenerativesystems biology activator that promotes self renewal and repair while activating cellular mechanisms that reduce the burden of AD pathologyBased on extensive preclinical discovery and IND enabling translational researcha Phasetrial was recently completed in which Allo was administered intravenously using a regenerative treatment regimenTo advance therapeutic development of Allo as a regenerative therapeuticthe project proposed herein addresses two critical barriers to clinical translatabilityFeasibility of chronic long term administration of Allo in an aged population with AD andOptimization of route of administration to promote patient complianceTo address these challengeswe propose to develop a novel microemulsion formulation of Allo to advance transdermal route of administrationAims of our SBIR project areDevelop a novel microemulsion Allo formulation in a transdermal patch delivery systemDetermine its in vitro permeability andEstablish the pharmacokinetics of this novel transdermal Allo microemulsionTransdermal formulations of Allo will advance clinical feasibility of chronic Allo treatment and patient therapeutic complianceResearch proposed herein is responsive to PASto develop and evaluate therapies toslow and or reverse the course of AD and NIA Strategic Plan translational objectives within Section Dto support the development of innovative therapies to treat AD ADRD PROJECT NARRATIVE Alzheimer s diseaseADis a progressive multifactorial disease affecting more thanmillion people worldwide and to dateno interventions have demonstrated substantial therapeutic efficacy to preventdelay or treat ADThe neurosteroid allopregnanoloneAllois under development for treatment of patients with AD has already demonstrated remarkable safety in Phase I clinical trials given once weekly by intravenous infusionThe purpose of this study is to develop transdermal microemulsion formulations of Allo which would significantly improve patient compliance and eventuallytheir overall quality of life