Alzheimerâs disease (AD) is a progressive multifactorial disease affecting more than 50 million people worldwide and is the most common dementia of late-life. To date, no interventions have demonstrated substantial therapeutic efficacy to prevent, delay or treat AD. Current thinking in the field embraces the complexity of AD pathophysiology, which has enabled a more diverse therapeutic pipeline targeting multiple aspects of the disease. The neurosteroid allopregnanolone (Allo) is under development as a regenerative therapeutic to regenerate the degenerated Alzheimerâs brain. Allo is an innovative, regenerative, systems biology activator that promotes self-renewal and repair while activating cellular mechanisms that reduce the burden of AD pathology. Based on extensive preclinical discovery and IND-enabling translational research, a Phase 1 trial was recently completed in which Allo was administered intravenously using a regenerative treatment regimen. To advance therapeutic development of Allo as a regenerative therapeutic, the project proposed herein addresses two critical barriers to clinical translatability: 1) Feasibility of chronic long-term administration of Allo in an aged population with AD and 2) Optimization of route of administration to promote patient compliance. To address these challenges, we propose to develop a novel microemulsion formulation of Allo to advance transdermal route of administration. Aims of our SBIR project are: 1. Develop a novel microemulsion Allo formulation in a transdermal patch delivery system. 2. Determine its in-vitro permeability and 3. Establish the pharmacokinetics of this novel transdermal Allo microemulsion. Transdermal formulations of Allo will advance clinical feasibility of chronic Allo treatment and patient therapeutic compliance. Research proposed herein is responsive to PAS 18-187 to develop and evaluate therapies to âslow and/or reverse the course of AD and NIA Strategic Plan translational objectives within Section D4 to support the development of innovative therapies to treat AD/ADRD.
Public Health Relevance Statement: PROJECT NARRATIVE Alzheimerâs disease (AD) is a progressive multifactorial disease affecting more than 50 million people worldwide and to date, no interventions have demonstrated substantial therapeutic efficacy to prevent, delay or treat AD. The neurosteroid allopregnanolone (Allo) is under development for treatment of patients with AD has already demonstrated remarkable safety in Phase I clinical trials given once weekly by intravenous infusion. The purpose of this study is to develop transdermal microemulsion formulations of Allo which would significantly improve patient compliance and eventually, their overall quality of life.
Project Terms: absorption; Address; Affect; Age; Age-Years; Aging; aging population; Allopregnanolone; Alzheimer's Disease; Alzheimer's disease related dementia; Animal Model; Animals; base; Brain; Caregivers; Chronic; Clinic Visits; Clinical; Clinical Data; clinical development; Clinical Trials; clinically translatable; Cognitive; Collaborations; commercialization; compliance behavior; Dementia; design; Detection; Development; Disease; Disease Progression; Dose; drug development; Drug Kinetics; effective therapy; Elderly; Ensure; Ethics; Excipients; Female; Formulation; Functional disorder; Gastrointestinal tract structure; High Pressure Liquid Chromatography; Home environment; Human; improved; In Vitro; in vivo; Incidence; Infusion procedures; innovation; Innovative Therapy; Intervention; Intravenous; intravenous administration; Intravenous infusion procedures; Lead; lead candidate; liver metabolism; male; Metabolism; Methods; Miniature Swine; Modeling; Natural regeneration; Neurodegenerative Disorders; Neurologic; neurosteroids; novel; novel therapeutic intervention; Oral; Pathology; Patients; Permeability; Persons; Pharmacologic Substance; Phase; Phase I Clinical Trials; Population; pre-clinical; Prevalence; prevent; Process; Quality of life; regenerative; regenerative therapy; repaired; Reproducibility; Research; research clinical testing; Risk; Route; Safety; self-renewal; Sex Differences; Small Business Innovation Research Grant; Solubility; Strategic Planning; System; Systems Biology; Target Populations; Testing; Therapeutic; therapeutic development; therapy development; Thinking; Toxicology; Translational Research; Treatment Efficacy; Treatment Pr
