Biomarker for Friedreich's Ataxia (BioFridA)

Study Overview
=================
Brief Summary
-----------------
International, multicenter, observational, longitudinal monitoring study to identify biomarker/s for Friedreich's Ataxia and to explore the clinical robustness, specificity, and long-term variability of these biomarker/s

Detailed Description
-----------------
An ataxia is neurological disorder of balance and coordination resulting from dysfunctions of the cerebellum. Friedreich's ataxia (FRDA) is most common ataxia in white population, with an estimated prevalence of 2-4 cases per 100,000 individuals. With an average age of onset of 10-15 years, the disease is characterized by dysarthria, deep sensory loss, hypertrophic cardiomyopathy, spinocerebellar ataxia, pyramidal weakness, diabetes mellitus, and skeletal abnormalities. FRDA is an autosomal recessive disorder caused by pathogenic variant/s in the FXN gene, which encodes the mitochondrial protein frataxin. In 98% of cases these are homozygous guanine-adenine-adenine (GAA) triplet repeat expansions in the ﬁrst intron of the FXN gene. The remaining cases are compound heterozygotes for a GAA repeat expansion plus a FXN point mutation or deletion. GAA repeat expansions suppress transcription of the FXN gene, leading to frataxin deﬁciency. Until now there is no FDA-approved therapy for FRDA, but potential agents for treatment are in developing phases. As such, especially antioxidants like idebenone are tested in clinical trials as FRTA medication, whereas another study identified p38 inhibitors as potential therapeutic agents. Various clinical rating scales including the Scale for the Assessment and Rating of Ataxia (SARA), Friedreich's Ataxia Rating Scale (FARS), and the International Cooperative Ataxia Rating Scale (ICARS) have been used as trial endpoints in FRDA, but these measurements have limited sensitivity to disease progression over 12 months. Furthermore, there are no validated, objective central or peripheral nervous system biomarkers of disease progression for use in clinical trials as intermediate endpoints. It is the goal of the BioFridA study to identify, validate, and monitor FRDA biomarker/s.

Official Title
-----------------
Biomarker for Friedreich's Ataxia: An International, Multicenter, Observational, Longitudinal Protocol

Conditions
-----------------
FXN Gene, FRDA, Hereditary Diseases

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent is obtained from the participant or parent/ legal guardian The participant is aged between 2 and 50 years of age The diagnosis of Friedreich's Ataxia (FRDA) is genetically confirmed by CENTOGENE Exclusion Criteria: Informed consent is not obtained from the participant and parent/ legal guardian The participant is younger than 2 years or older than 50 years of age The diagnosis of FRDA is not genetically confirmed by CENTOGENE

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Friedreich's Ataxia<br>Participant diagnosed with Friedreich's Ataxia aged between 2 and 50 years of age | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of Friedreich's Ataxia biomarker/s | All samples will be analyzed for the identification of potential biomarkers via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploring the clinical robustness, specificity, and long-term variability of Friedreich's Ataxia biomarker/s | All samples will be analyzed for the identification of potential biomarkers via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Friedreich's Ataxia, Biomarker