# Natural History of Friedreich ataxia in children

> **NIH FDA R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $399,482

## Abstract

Abstract
Friedreich’s ataxia (FRDA) is the most common form of hereditary ataxia, affecting approximately 1 in every
50,000 people in the United States and Europe. Symptoms typically begin between the ages of 5 and 15 years
and worsen over time. The pathophysiology of FRDA reflects the deficiency of the protein frataxin. Reduced
frataxin levels impair the function of mitochondrial iron-sulfur-cluster-containing enzymes and ability to produce
ATP. Recently, amelioration of frataxin deficiency by gene therapy in mouse models of FRDA has produced
impressive benefit in reversing the phenotype, providing an evidenced-based approach for treatment of FRDA
patients. Mitigation of mitochondrial dysfunction also represents a valid therapeutic approach. However, if
attempts at these therapies were made today, they would be limited by the inability to assess the human biology
of FRDA in detail, as well as the inability to target therapies to the most biologically responsive individuals,
children. To achieve this goal, we will study the natural history of FRDA in children, to understand the course of
disease activity in this age group.
In the first aim, we will assess potential measures of disease progression in the youngest subjects with FRDA
(n=100 at 3 sites) These will include specific revisions and modifications of timed walks (in order to identify a test
more suitable for use in young individuals, and an automated measure of upper extremity coordination (the
CCFS) that is useful in older FRDA subjects. In aim 2 we will assess biochemical measures of frataxin deficiency
and downstream metabolic function, and understand their utility in serial monitoring.in children with FRDA.
Peripheral samples (blood, buccal cells, isolated platelets) will be obtained from a large heterogeneous cohort
of subjects with FRDA (n=100 at 3 sites). We will then assay the primary biomarker of disease severity, frataxin
level, in the samples with a newly devised mass spectrometry-based assay to understand how such levels reflect
disease status. In parallel, we will examine mitochondrial-derived alterations in metabolic pathways in platelets
to examine events downstream from frataxin deficiency. Finally we will examine physiological tests (motor
evoked potentials, Cr-CEST of muscle) that can link clinical parameters with biochemical measurements.
Cumulatively these aims will define the utility of such approaches in clinical measurement of FRDA in children,
and validate such approaches as the definitive measures needed for design of informative trials in children with
FRDA.

## Key facts

- **NIH application ID:** 10237179
- **Project number:** 5R01FD006029-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** DAVID ROBINSON LYNCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $399,482
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237179

## Citation

> US National Institutes of Health, RePORTER application 10237179, Natural History of Friedreich ataxia in children (5R01FD006029-05). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10237179. Licensed CC0.

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