# Synthetic molecules to stimulate the expression of Frataxin to ameliorate Freidreichs Ataxin

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $608,525

## Abstract

PROJECT SUMMARY/ABSTRACT
Friedreich's ataxia (FRDA/FA) is the most commonly inherited autosomal recessive neurodegenerative disease
for which there is no cure. This debilitating and ultimately lethal disease occurs due to reduced expression of
frataxin (FXN), a nuclear encoded protein that plays a role in iron metabolism in mitochondria. Homozygous
expansion of GAA triplet repeats in the first intron of FXN silence mRNA synthesis. The resulting FXN protein
deficiency leads to progressive neurodegeneration, hypertrophic cardiomyopathy and even diabetes mellitus. A
novel class of synthetic transcription elongation factors (Syn-TEFs) that target GAA repeat expansions in FXN
and actively stimulate Pol II function across the silenced gene were recently developed by our group. In patient-
derived cells, Syn-TEF1 restores FXN to levels observed in healthy individuals. The premise that underlies this
proposal is that systematic evaluation of the Syn-TEF responsive changes in the epigenetic landscape and/or
the formation of stable unusual DNA structures will reveal the extent to which of these mechanisms contribute
to FXN silencing in patient-derived cells. This understanding will result in more mechanistically-guided design of
the next generation precision-tailored Syn-TEFs. Moreover, testing Syn-TEFs in cell types where FXN deficiency
results in ataxia and morbidity is a first step toward the development of genome-targeted precision therapeutics.

## Key facts

- **NIH application ID:** 9930685
- **Project number:** 5R01NS108376-09
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** ASEEM Z ANSARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,525
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930685

## Citation

> US National Institutes of Health, RePORTER application 9930685, Synthetic molecules to stimulate the expression of Frataxin to ameliorate Freidreichs Ataxin (5R01NS108376-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930685. Licensed CC0.

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