# Neurobehavioral and biochemical outcome measures in Rett syndrome rodent models

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $564,840

## Abstract

Rett syndrome (RTT) is a devastating X-linked neurodevelopmental disorder and one of the leading causes
of intellectual disability and developmental regression in girls. RTT is caused by loss-of-function mutations in
the gene encoding the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) and several mouse
models that recapitulate features of the disease have been created by targeted disruption of the homologous
mouse gene, Mecp2. There is a crucial need to develop therapies for RTT, however, the best practices and
standards for performing preclinical trials – which will be essential for prioritizing and validating therapies that
are to be advanced to human trials – have not yet been determined. To address this need, we propose studies
in well-chosen RTT rodent models that consider factors such as sex, genetic strain background, species, and
age during the natural course of disease. By defining the onset and progression of translationally-relevant
neurobehavioral phenotypes and co-occurring plasma metabolite alterations, we will bridge behavioral
outcome with potential biomarkers for RTT. In addition, we will use genetic and pharmacological strategies to
examine how biomarkers may change with disease improvement to further classify markers that may predict
treatment response. Finally, to optimize the clinical relevance of our results, we will test metabolites identified
from our animal studies in RTT individuals. Our goal is to identify the phenotypic and biochemical alterations in
Mecp2 rodents that can serve as outcome measures in preclinical studies in animal models and eventual
clinical studies in humans. We hypothesize that abnormalities in plasma metabolites that co-occur with disease
onset, become markedly altered with disease progression and conversely normalized with disease
improvement will serve as the most useful biomarkers with the highest degree of translatability. The Specific
Aims of the proposal are i) to define and validate translationally-relevant phenotypes and co-occurring changes
in plasma metabolites among Mecp2 rodents, ii) to examine alterations in behavior and metabolite profile
during disease improvement, and iii) to evaluate the predictive validity of Mecp2 rodent biochemical alterations
in RTT. The unique features of the proposed work should maximize its utility to the RTT research community
and accelerate preclinical studies in RTT models. Taken together, these studies will provide the indispensable
ground-work for endeavors to identify from rodent models the interventions that have the highest likelihood of
translating into effective human therapies. Regardless of the outcome, the results will define the direction that
the field must take, either underscoring the need for new approaches, or promoting the most effective
preclinical research practices using existing rodent models.

## Key facts

- **NIH application ID:** 9980446
- **Project number:** 5R01HD083181-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Jeffrey L Neul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $564,840
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980446

## Citation

> US National Institutes of Health, RePORTER application 9980446, Neurobehavioral and biochemical outcome measures in Rett syndrome rodent models (5R01HD083181-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980446. Licensed CC0.

---

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