# TCF4 in Pitt-Hopkins syndrome

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $337,260

## Abstract

PROJECT SUMMARY
Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by loss of speech, EEG
abnormalities, seizures, motor impairments, and severe intellectual disabilities. Unfortunately, there are no
treatments for its core symptoms. PTHS is caused by haploinsufficiency of TCF4, a transcription factor that
regulates hundreds of genes, making it nearly impossible to therapeutically address the full phenotypic
spectrum of the disorder by targeting downstream molecular pathways. Ideally, PTHS would be treated at its
roots, by augmenting the expression of the intact TCF4 gene copy to normalize gene expression levels. We
hypothesize that small molecules capable of upregulating TCF4 expression during early postnatal
development, and perhaps into adulthood, will correct PTHS phenotypes. To develop an informed therapeutic
intervention strategy and to identify TCF4 activators for eventual clinical trials, we will complete three Aims: (1)
establish the biodistribution of TCF4 to guide therapeutic delivery, (2) assess phenotypic rescue with early- or
late-onset normalization of TCF4, and (3) identify approaches to increase TCF4 levels. We have developed
and validated powerful tools to facilitate each of these Aims, which are integral to guiding the clinical
development of genetic normalization treatments for PTHS.

## Key facts

- **NIH application ID:** 10023965
- **Project number:** 5R01NS114086-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** BENJAMIN D PHILPOT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,260
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023965

## Citation

> US National Institutes of Health, RePORTER application 10023965, TCF4 in Pitt-Hopkins syndrome (5R01NS114086-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10023965. Licensed CC0.

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