# Targeting the neurobiology of restricted and repetitive behaviors in children with autism using N-acetylcysteine

> **NIH NIH R00** · STANFORD UNIVERSITY · 2023 · $249,000

## Abstract

PROJECT SUMMARY
The goals of this study are to target the neurobiology underlying restricted and repetitive behaviors (RRB) in
children with autism spectrum disorder (ASD) using N-acetylcysteine (NAC), a well-tolerated nutritional
supplement and glutamatergic modulator that has exhibited efficacy for reducing RRB severity in recent
preliminary trials. The goals of this career developmental award are to learn the theoretical principles and develop
practical application techniques for proton spectroscopy (1H MRS) and electroencephalography (EEG)
approaches in children with neurodevelopmental disorders, learn clinical trial methodologies and develop skills
for examining treatment efficacy in controlled trials, and learn advanced statistical modeling techniques for
assessing complex treatment-related outcomes in pediatric populations. The ultimate overarching goal is to
support a promising early career investigator in transitioning to an independent research position. To achieve
these goals, we will (Aim 1) acquire 1H MRS and EEG data from children with ASD who exhibit severe RRB and
examine the ability of NAC to modulate excitatory signaling in cortico-striatal circuits (CSC) in a single dose
challenge study (NAC and placebo). We will also (Aim 2) examine the efficacy of NAC for improving RRB in a
12-week randomized controlled trial and (Aim 3) assess the ability of neurobiological measures of excitatory
signaling (1H MRS and EEG) to predict treatment response. CSC are a salient treatment target because CSC
contribute to RRB in mouse models of ASD and exhibit relationships with RRB severity in children with ASD.
Altered excitatory signaling in CSC regions have also been reported in children/adults with ASD, and most
importantly, NAC can modulate glutamatergic signaling in CSC regions. Thus, excitatory (i.e. glutamatergic)
signaling in CSC in ASD may contribute to the severity of RRB, at least for some individuals, and modulation
with NAC may confer some clinical benefits, especially for children with elevated levels at baseline. We expect
that children with ASD who receive NAC will exhibit a larger reduction in 1H MRS and EEG measures of
glutamatergic signaling compared to children who receive placebo, which will be associated with a larger
reduction in RRB severity following 12 weeks of treatment with NAC compared to placebo. We expect that
baseline measures will also be able to accurately predict which children respond to NAC and will explore the
effects of NAC on different subtypes of RRB, which may be due to different neurobiological alterations. The
findings from this research will support the efficacy of NAC for the treatment of RRB and shed light on the
mechanisms of action underlying NAC-mediated improvements. This is particularly important because there are
currently no drug treatments for the core symptoms of ASD, including RRB, and severe RRB are associated with
management challenges and barriers to adaptive learning. With this training, ...

## Key facts

- **NIH application ID:** 10758985
- **Project number:** 4R00HD101702-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** John Patrick Hegarty
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758985

## Citation

> US National Institutes of Health, RePORTER application 10758985, Targeting the neurobiology of restricted and repetitive behaviors in children with autism using N-acetylcysteine (4R00HD101702-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10758985. Licensed CC0.

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