FRDA, FXN Gene, Hereditary Diseases
Conditions
Keywords
Friedreich's Ataxia, Biomarker
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.
Interventions
None listed
Sponsors
CENTOGENE GmbH Rostock
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Months to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Friedreich's Ataxia biomarker/s | 36 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exploring the clinical robustness, specificity, and long-term variability of Friedreich's Ataxia biomarker/s | 36 months | 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. |
Countries
Lebanon
Outcome results
None listed