# Frataxin measurement for clinical trial readiness in Friedreich ataxia

> **NIH NIH R21** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $204,600

## 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.
However, if attempts at reversal of frataxin deficiency were made today, they would be limited by
the inability to assess frataxin levels in detail, as well as the inability to target therapies to the
most biologically responsive individuals. To achieve this goal, we will validate the rigorous
measurement of frataxin in larger cohorts to understand how it reflects disease activity.
In the first 2 aims, we will test improved measures of frataxin deficiency and downstream
metabolic function, and understand their utility in therapeutic monitoring. Peripheral samples
(blood, buccal cells, isolated platelets, muscle) will be obtained from a large heterogeneous cohort
of subjects with FRDA (n=200, n=20 for muscle). We will then assay the primary biomarker of
disease severity, frataxin level, in the samples with a newly devised mass spectrometry based
assay in order to understand the sensitivity of the assay and how such levels reflect disease
status. In the second aim, we will examine mitochondrial-derived alterations in metabolic
pathways in platelets and muscle to examine events downstream from frataxin deficiency. In Aim
3, we will reevaluate long term natural history data from already established clinical instruments
in the context of frataxin levels. Such data is available for a large >500 person cohort including
the 200 who provide samples for the present study, and can be used to understand the
relationship between frataxin levels and clinical status. Cumulatively these aims will define the
utility of frataxin levels in clinical measurement of FRDA, and validate such approaches as
definitive measures needed for design of informative trials of frataxin restoration.

## Key facts

- **NIH application ID:** 9986922
- **Project number:** 5R21TR003035-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** DAVID ROBINSON LYNCH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,600
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986922

## Citation

> US National Institutes of Health, RePORTER application 9986922, Frataxin measurement for clinical trial readiness in Friedreich ataxia (5R21TR003035-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986922. Licensed CC0.

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