# Novel Intranasal Formulations of Allopregnanolone, a Regenerative Therapeutic for Alzheimer's Disease

> **NIH NIH R43** · NEUTHERAPEUTICS, LLC · 2023 · $505,836

## Abstract

Project Summary/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 recommendati...

## Key facts

- **NIH application ID:** 10698555
- **Project number:** 1R43AG081024-01A1
- **Recipient organization:** NEUTHERAPEUTICS, LLC
- **Principal Investigator:** ROBERTA EILEEN BRINTON
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $505,836
- **Award type:** 1
- **Project period:** 2023-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698555

## Citation

> US National Institutes of Health, RePORTER application 10698555, Novel Intranasal Formulations of Allopregnanolone, a Regenerative Therapeutic for Alzheimer's Disease (1R43AG081024-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10698555. Licensed CC0.

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