# An RNA-based approach to intranasal delivery of neuropeptides to the brain

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $254,250

## Abstract

PROJECT SUMMARY
The health burden of social disabilities and mood disorders including autism, depression, and anxiety is
escalating rapidly, with an estimated cost of more than $500 billion per year. Despite the burden and the
immense cost, the availability, efficacy, and tolerability of pharmacotherapies to treat these disorders are both
limited and suboptimal. Neuropeptides are an important class of modulators for affective behaviors that have
been widely implicated in mediating social behavior, stress, and anxiety. As a result, they have received
considerable attention as possible therapeutics for social and mood disorders. The intranasal route is one of
few potential routes for neuropeptide brain delivery. Several studies, however, have shown that the fraction of
neuropeptide doses reaching the cerebral spinal fluid following intranasal neuropeptide administration is very
low. This outcome could be attributed to the fact that neuropeptides have short half-lives and that only limited
solution volumes can be administered intranasally. Thus, to date, testing of whether neuropeptides may be
effective treatments for social and mood disorders has been limited by the difficulty of administering these
molecules to the brain effectively. The objective of the proposed study is to establish a novel, RNA-based
approach to efficiently deliver neuropeptides to the brain through intranasal administration. As a proof of
concept, we will test the efficacy of our RNA-based intranasal approach to deliver the OXT peptide to the rat
brain. We have recently validated a first rat model for autism, the Shank3-deficient rat, and demonstrated that
OXT improves social and attentional deficits in this rat. To test the functionality of the delivered OXT, we will
leverage the Shank3-deficient rat model and assess the ability of the OXT, delivered intranasally using our
RNA-based approach, to reverse the social behavior deficits in this model. The proposed study will be the first
ever to test the efficacy of an RNA-based approach to delivering a functional neuropeptide to the brain. It will
lay the foundation for future studies that will test the efficacy of our novel platform to deliver several other
neuropeptides, alone or together, that are of potential therapeutic value for brain-based disorders. Importantly,
findings from this study will set the ground for the development of a novel and innovative clinically-relevant
therapeutic approach that is urgently needed to overcome the limitations of neuropeptide delivery to the human
brain.

## Key facts

- **NIH application ID:** 9882520
- **Project number:** 5R21MH119502-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Hala Harony-Nicolas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882520

## Citation

> US National Institutes of Health, RePORTER application 9882520, An RNA-based approach to intranasal delivery of neuropeptides to the brain (5R21MH119502-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9882520. Licensed CC0.

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