Novel intranasal formulations of allopregnanolone,?a?regenerative therapeutic for alzheimer's disease

Ended Project Grant Awarded Last action

Award ID
R43AG081024
Recipient
Awarding agency
Obligated
$342,879

Award facts

Assistance listing
93.866 Aging Research
Completion date
Originally
Place of performance
Arizona, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Alzheimer's 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 for ad. Allo is an innovative, regenerative, systems biology activator that promotes regeneration and repair while activating mechanisms that reduce the burden of ad pathology. Based on extensive preclinical discovery and IND-enabling translational research, a phase 1 clinical trial was completed and established safety for allo 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) route of administration optimization to promote patient compliance. To address these challenges, we propose to develop a novel allo formulation to enable an intranasal route of administration. A transmucosal formulation of allo advances clinical use in an aged ad population while also addressing first-pass metabolism constraints that limit oral bioavailability of allo. Aims of the sbir entitled novel intranasal formulations of allopregnanolone, a regenerative therapeutic for ad are: aim 1: develop allo formulations for in delivery in collaboration with medpharm; aim 2: establish pharmacokinetics of allo-in formulations in brain, olfactory bulb and plasma after administration to a RAT. To achieve these aims, experts in formulation (medpharm) will develop a solution or a suspension of allo for in delivery. To achieve this objective, medpharm will: 1. Perform pre-formulation, proof of concept formulation development and stability assessments of allo formulations and assess achievable concentrations of allo to develop up to 5 solution or suspension formulation nasal sprays. 2. Conduct in vitro reconstituted nasal epithelial (RNE) permeation testing using primary human nasal epithelial cells which exhibit mucus production, ciliary activity, tight junctions, and barrier function. The 3 most promising formulations will advance to aim 2 for pharmacokinetic analysis in a RAT model. In vivo analyses will be conducted in both female and males to investigate potential SEX differences in pharmacokinetics of intranasal absorption. This research is responsive to PAS-19-316 to "conduct research leading to the development of innovative products and/or services that may advance progress in preventing and treating ad and ad-related dementias (adrd)" and "address recommendations and milestones for ad/adrd research from the national alzheimer's project act."

Transactions

Action Obligated Date
Amendment -$162,957
Amendment $0
Original award $505,836

Quick answers

Who received award R43AG081024?

R43AG081024 was awarded to Neutherapeutics LLC by National Institute on Aging (National Institutes of Health) on July 15, 2023.

How much is award R43AG081024 worth?

$342,879 has been obligated on R43AG081024.

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