# Circulating Organ-enriched microRNAs as biomarkers of Rett Syndrome

> **NIH NIH R43** · DIAMIR, LLC · 2020 · $387,616

## Abstract

SUMMARY
Rett syndrome (RTT) is a rare X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene.
The disease affects females almost exclusively, since male fetuses with a MECP2 mutation usually die before
birth. Affected females appear normal at birth; disease onset is typically evident by 6-18 months and is
characterized by neurological regression, motor stereotypies, irregular breathing, and other handicaps. Clinical
severity appears to depend on multiple factors, including the type of MECP2 mutation, skewing of the X-
inactivation and likely genetic modifiers of MECP2. Although diagnostic MECP2 genetic testing is available for
RTT, peripheral biomarkers of RTT, including minimally invasive, blood-based indicators of disease severity and
progression, are lacking. DiamiR, a molecular diagnostics company, has developed proprietary platform
technology for early detection and monitoring of pathophysiological processes based on analysis of circulating
organ-enriched, including brain-enriched, microRNAs (miRNAs) in plasma. Studies conducted to date at the
company resulted in identification of promising miRNA biomarker candidates for neurodegenerative and other
diseases, and here we propose extending the use of our technology to establish miRNA biomarkers of RTT.
Loss of MECP2 results in synaptic dysfunction and marked dysregulation of miRNAs in the brain. We
hypothesize that circulating miRNAs enriched in different brain regions, present in synapses/neurites, and
detectable in plasma can detect pathophysiological processes associated with RTT development. In addition,
analysis of levels of miRNAs enriched in liver, lung and muscle can be reflective of RTT associated changes in
these tissues. An “miRNA pair” approach is used for data normalization, and a biomarker candidate is comprised
of a ratio of two miRNAs. Two-three miRNA pairs are combined into a miRNA classifier for higher accuracy.
Preliminary studies performed with four murine models and human patients identified miRNA pairs and classifiers
differentiating both RTT mouse models from wild-type mice and RTT patients from age-matched control (AMC);
certain miRNA pairs were common to mice and humans, indicating the similarity between the underlying
pathological processes. The current study will be performed using plasma samples collected at the Rett Center
at Montefiore Medical Center. Specific aims include: (1) assessing the feasibility of differentiating RTT from AMC
by plasma levels of 38 pre-selected circulating miRNAs enriched in organs/tissues affected by RTT (brain, liver,
lung, muscle) (60 RTT/60 AMC); and (2) evaluating the potential of circulating miRNAs for predicting disease
severity and monitoring disease progression by analysis of plasma levels of the previously studied 19 miRNAs
in the longitudinal set of samples collected 3 years later from the same study participants (30 RTT/30 AMC).
SBIR Phase II will involve larger clinical studies to validate miRNA biomarker ...

## Key facts

- **NIH application ID:** 9907604
- **Project number:** 1R43NS115212-01
- **Recipient organization:** DIAMIR, LLC
- **Principal Investigator:** SAMUIL R UMANSKY
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,616
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-03-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9907604

## Citation

> US National Institutes of Health, RePORTER application 9907604, Circulating Organ-enriched microRNAs as biomarkers of Rett Syndrome (1R43NS115212-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9907604. Licensed CC0.

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