# Anti NMDA Receptor antibodes in adult brain dysfunction and fetal brain development: lessons from lupus

> **NIH NIH P01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $2,858,960

## Abstract

PPG OVERALL
Abstract: Neuropsychiatric lupus (NPSLE) is a common and debilitating manifestation of
Systemic Lupus Erythematosus (SLE). For over a decade, we have been studying the
contribution of a subset of anti-DNA antibodies that cross reacts with the N-methyl D-aspartate
receptor, termed DNRAb, to cognitive impairment in NPSLE, and to impairments in fetal health
of DNRAb+ mothers. We have developed a mouse model in which we have now shown that
DNRAb, when they penetrate the hippocampus, cause acute neuronal death subsequently
leading to persistent microglial activation, neuronal dendritic loss, and cognitive impairments.
Suppression of microglial activation by angiotensin converting enzyme (ACE) inhibitors leads to
a restoration of neuronal integrity and cognitive function. Using the same model, we have
demonstrated that maternal DNRAb cause death of female fetuses and cognitive impairment in
male offspring through transplacental transport. We have demonstrated in subjects with SLE
that memory impairment is associated with increased titers of DNRAb and that a reduced
microstructural integrity of parahippocampal fibers also associates with DNRAb. We proposed
to continue to study both the mouse model and SLE patients, to understand the mechanisms of
microglial activation and how ACE inhibitors restore neuronal integrity. We will determine how
DNAbs alter male and female fetal brain development. We will assess microglial activation and
loss of blood brain barrier integrity in SLE patients and the association of these abnormalities
with elevated titers of DNRAb.
These studies have already led to a funded clinical trial of ACE inhibitors in non-focal central
nervous system manifestations of NPSLE, and have the potential to reveal additional potential
therapeutic strategies.

## Key facts

- **NIH application ID:** 10885138
- **Project number:** 5P01AI073693-15
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Betty Diamond
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,858,960
- **Award type:** 5
- **Project period:** 2008-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885138

## Citation

> US National Institutes of Health, RePORTER application 10885138, Anti NMDA Receptor antibodes in adult brain dysfunction and fetal brain development: lessons from lupus (5P01AI073693-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885138. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*