Biomarkers in Friedreich's Ataxia

Study Overview
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Brief Summary
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The purpose of this project is to characterize measures of cardiac performance and neuromuscular physiology in FA patients using novel techniques, including echocardiography and magnetic resonance imaging (MRI), metabolic exercise testing, and neurophysiological outcomes.

Detailed Description
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Friedreich's ataxia (FA) is an autosomal recessive disease caused by a mutation in the frataxin gene (FXN). Although rare, FA is the most common form of hereditary ataxia, affecting 1 in every 50,000 people in the United States. Currently, palliative therapies are the only treatment for FA patients. However, current gene therapy efforts in other neuromuscular diseases have positioned the investigator's research program to extend these discoveries and techniques to FA. As new therapies become available for clinical application, it is crucial to identify non-invasive outcomes measures of cardiac and neuromuscular performance with adequate sensitivity to detect the impact of treatments.

Official Title
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Biomarkers in Friedreich's Ataxia

Conditions
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Friedreich's Ataxia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetic diagnosis of Friedreich's ataxia by DNA sequencing, mutational analysis or protein assay OR be a healthy subject with no evidence of a neuromuscular disorder Between the ages of 8 and 70 (inclusive) Are able to tolerate metabolic exercise testing Are stable on cardiac medication regimen for 3 months prior to screening Exclusion Criteria: Presence of unstable heart disease Receipt of cardiac transplant Any concurrent medical condition which, in the opinion of the investigators, would make the subject unsuitable for the study

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Affected with Friedreich's ataxia<br>Friedreich's ataxia patients aged 8 to 70 (inclusive). Assessments will include collection of genetic mutation reports, cardiac and exercise MRI, echocardiogram, the Friedreich's Ataxia Rating Scale (FARS), exercise testing with a recombinant bike and/or hand ergometer, pulmonary function testing, and gait analysis. Optional labs include a blood draw, skin biopsy, and/or muscle biopsy. | |
| Healthy controls<br>Health controls aged 8 to 70 (inclusive). Assessments will include cardiac and exercise MRI, echocardiogram, the Friedreich's Ataxia Rating Scale (FARS), exercise testing, hand ergometer for exercise testing, pulmonary function testing, gait analysis, and an optional blood draw. | |
| Carriers of Friedreich's ataxia<br>An obligate carrier aged 18 to 70 (inclusive) of the abnormal Friedreich's ataxia gene by being a parent of a child with Friedreich's ataxia. No assessments are to be conducted. Optional labs include a blood draw, skin biopsy, and/or muscle biopsy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac MRI | Cardiac MRI will be used to characterize cardiac morphology and function. | Baseline and Follow-Up Visits | 
| Echocardiogram | Echocardiogram will be used to characterize cardiac morphology and function. | Baseline and Follow-Up Visits | 
| Friedreich's Ataxia Rating Scale (FARS) | FARS scores describe specific neurological impairments in FA. | Baseline and Follow-Up Visits | 
| Metabolic exercise testing | Metabolic exercise testing will be performed on either a recumbent bike or hand ergometer and will measure the maximal amount of exercise the subject is able to perform. | Baseline and Follow-Up Visits | 
| Scale for the Assessment and Rating of Ataxia (SARA) | Clinical scale assessing impairment levels in cerebellar ataxia | Baseline and Follow-Up Visits | 
| Muscle Biopsy | The muscle sample will be used to evaluate Frataxin quantification | Baseline | 
| Skin Biopsy | Analyses to peripheral tissue used to find out how Friedreich's Ataxia develops. | Baseline | 
| 9-Hole-Peg Test | Assesses upper extremity function and motor coordination. | Baseline and Follow-Up Visits | 
| Pulmonary Function Testing | Breathing tests to assess lung strength and function. | Baseline and Follow-Up Visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ataxia, neuromuscular