Research Resources

Preclinical Research Resources

FARA-funded research has facilitated the discovery and development of research resources such as animal models, cell models, antibodies, biorepositories etc. We are grateful to the discovery scientists who have worked hard to bring us these important assets and continue to give to the community by sharing their results, knowledge, expertise and resources. It is our goal to promote collaboration throughout the research community by communicating with the discovery, translational and clinical scientists and facilitating their access to such resources.

The Friedreich’s Ataxia Cell Line repository (FACLR) at UT Southwestern https://www.utsouthwestern.edu/labs/napierala/cell-line/ contains FRDA and control fibroblast and iPSC lines, including isogenic CRISPR/Cas9-edited paired lines.

Please view the PDF below for more information.

Clinical Research Resources

FARA-funded research has facilitated the discovery and development of research resources such as animal models, cell models, antibodies, biorepositories etc. We are grateful to the discovery scientists who have worked hard to bring us these important assets and continue to give to the community by sharing their results, knowledge, expertise and resources. It is our goal to promote collaboration throughout the research community by communicating with the discovery, translational and clinical scientists and facilitating their access to such resources.

Please view the PDF below for more information.

Mouse Models in Friedreich's ataxia

FARA is grateful to the FA researchers who have created and characterized FA mouse models. FARA collaborates with the Jackson Laboratory (JAX), Brunel University (UK), Erasme University (Belgium), Murdoch Children's Research Institute (Australia), IGBMC (France), and UCLA (USA) to make mouse models of Friedreich's ataxia (FRDA) available to the greater research community. FARA has partnered with JAX to centralize and expedite sharing of existing FA mouse models and to characterize those models. In addition, JAX has ongoing work to develop and make new models available to the Friedreich's ataxia community. Twelve mouse models are now available for use at Jackson Laboratories, and three additional models are available from IGBMC, and one through UCLA.

Please view the PDF below for more information.

Friedreich Ataxia -Omic Datasets

FARA is grateful to the research community for continued characterization and subsequent data sharing of datasets from Friedreich ataxia patient samples and animal and cell-based models.

Please view the PDF below for more information.

Measurement of Frataxin

Friedreich's Ataxia is caused by low levels of the protein frataxin, a consequence of mutations in the frataxin gene. Many potential therapies disease aim to increase levels of frataxin, targeting the root cause of the disease. Thus, sensitive, accurate and quantitative measurement of frataxin is an important biomarker in drug development, while understanding protein levels is also important in basic research. Several frataxin assays have been developed with different characteristics, which can be used for different contexts of use both in vitro and in vivo.

A paper was published in 2019 summarizing how different frataxin antibodies perform on human and animal samples. This paper may be found at https://www.sciencedirect.com/science/article/pii/S0022175919301097.

Please view the PDF below for more information.

Diagnosis of FA

Genetic testing has been the clinical standard for diagnosis of Friedreich's Ataxia since the gene was identified in the late 1990's. There is little published data on the time it takes for an individual to receive correct diagnosis. In this poster, we have used data from two sources (the Collaborative Clinical Research Network and a survey of patients and families) to evaluate the time to diagnosis—and its influencing factors—for adult and non-adult individuals with Friedreich's Ataxia (FA).

- Click the Poster to enlarge -

The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), has developed Friedreich's Ataxia (FA) Common Data Elements (CDEs) for use in clinical research. The NINDS recently assembled an external working group of experts, the FA CDE Working Group, to develop “Version 1.0” of the Friedreich's Ataxia CDEs and they are now ready for use in Friedreich's Ataxia clinical research community.

Friedreich's Ataxia CDE Standards Version 1.0

The NINDS CDE Web site fully describes the NINDS CDE Project and its goals. In summary, the CDE Project aims to develop content standards, both generic and disease-specific, that enable clinical investigators to systematically collect, analyze, and share data across the research community. The NINDS first convened the Friedreich's Ataxia CDE Working Group in June 2010. Over a one-year period the Friedreich's Ataxia CDE Working Group identified and defined a catalog of CDEs investigators can choose from when assembling their clinical study materials. The Friedreich's Ataxia CDE Working Group has not attempted to define the complete universe of variables a clinical study will collect; rather, their goal has been to isolate elements that will be useful across multiple FA clinical studies.

To develop the Friedreich's Ataxia (FA) CDEs, the FA CDE Working Group divided into subgroups to focus on identifying and defining data elements in the domains of:

• Ataxia and Performance Measures
• Biomarkers
• Cardiac and Clinical Outcomes
• Demographics, Medical History/ Prior Health Status, Laboratory Tests/ Vital Signs

Scientific Reference
Mov Disord. 2012 Dec 12. doi: 10.1002/mds.25201. [Epub ahead of print]
Common data elements for clinical research in Friedreich's ataxia
Lynch DR, Pandolfo M, Schulz JB, Perlman S, Delatycki MB, Payne RM, Shaddy R, Fischbeck KH, Farmer J, Kantor P, Raman SV, Hunegs L, Odenkirchen J, Miller K, Kaufmann P


FARA encourages all investigators doing clinical research studies in FA to consult these guidelines. The FA CDEs include case report form (CRF) modules, standardized data element definitions, and instructions intended to expedite the development of data collection tools. There is also significant gain from the ability to share and compare data across studies – these common data elements are a platform ensuring uniformity in data collection across multiple distinct studies so that later comparative analyses may be performed.

Overview of biomarkers and endpoints for FA

FARA has worked with the Friedreich’s ataxia (FA) community through the years to help develop endpoints and biomarkers for use in clinical trials. The Collaborative Clinical Research Network for FA (CCRN) was initially formed to develop and test a neurological rating scale, the Friedreich’s Ataxia Rating Scale, or FARS along with a disability rating scale, activities of daily living scale and functional measures1,2,. This scale is used to measure disease progression in patients, and a subscore (mFARS) has been accepted as an endpoint for late stage trials in FA. Data for this scale, alongside other outcomes, has now been collected by the CCRN for over 12 years3. Other rating scales and functional endpoints have also been used in trials, and data has been collected in natural history studies. More recently, a need for biomarkers for various contexts of use has been recognized, and data has been collected for a variety of such markers.

Please view this PDF for more information.

To learn more about the modified Friedreich's Ataxia Rating scale view the - mFARS Info Sheet.

Assays to Measure Downstream Consequences of Frataxin Deficiency

In Friedreich's ataxia (FRDA), large expansions of the intronic, triplet GAA repeat in the FXN gene result in reductions in the protein product Frataxin (FXN). FXN is a small, highly conserved mitochondrial protein, whose loss impairs iron-sulfur cluster (ISC) biosynthesis. In FRDA patients, disrupted ISC biosynthesis causes maladaptive alterations in cellular processes downstream of ISC biogenesis that manifest as neurodegeneration, hearing and vision loss, diabetes, and fatal cardiomyopathy. The extent of GAA expansion and consequent FXN loss strongly correlate with age of disease onset, disease severity, and age at death in FRDA patients.

Direct assessment of FXN levels, particularly in affected tissues that are difficult to access, has been challenging for the field, so researchers have developed assays to measure downstream consequences of reduced FXN expression and function. These include activity of various ISC containing proteins and assays for metabolic changes related to reduction in ISC protein activities, as well as oxidative damage and mitochondrial function deficits, as described below. Additional assays are also being developed that relate to other processes disrupted in FRDA cells.

This is a list of assays that have been used as downstream measures of FXN, but many other markers are also used.

Please view the PDF below for more information.

Friedreich's Ataxia Integrated Clinical Database (FA-ICD)

FA-ICD Mission:
Launched in February 2019, the Friedreich’s Ataxia Integrated Clinical Database (FA-ICD) is designed to catalyze and accelerate Friedreich’s ataxia (FA) research and drug development by curating and standardizing FA clinical trial and natural history data into CDISC format, and making this data publicly available to qualified researchers. These researchers can access and analyze data in aggregate, or filter and view individual de-identified patient-level data from four clinical trials and a large FA natural history study. Additional data may be available in the future.

FA-ICD Partnership:
This initiative represents a collaborative partnership between the Friedreich’s Ataxia Research Alliance (FARA) and Critical Path Institute (C-Path), with a goal of expanding the FA-ICD platform by engaging with other data contributors to secure additional datasets.

FA-ICD Content:
Approved researchers can access de-identified patient-level data from placebo arms of four clinical trials and a natural history study, including:

Trial data is anonymized in the database, so researchers will not be able to ascertain which data came from which trial, and they will not be able to identify participants in any study.

FA-ICD also contains data from the FARA-funded Friedreich’s Ataxia Clinical Outcome Measure Study conducted by the Collaborative Clinical Research Network (CCRN). The CCRN has collected natural history data on over 1,000 FA patients. The natural history for over 500 patients goes back more than 5 years and has more than 250 patients with baseline visits before 18 years of age.

Information about these studies may be found by clicking HERE.

Additional data is expected to be made available in the future.

FA-ICD Access:
FA-ICD catalogs completed FA clinical trials and natural history data and makes it available to qualified researchers. Access to the patient level data is by request only and subject to review and approval by the FA-ICD Steering Committee. To request access, you must agree to the Terms and Conditions for Use and submit a Request for Access application detailing how the data will be used, who will access the data and any plans for publishing work informed by the data. The Terms and Conditions can be accessed HERE.

For more information on FA-ICD, including how your organization can contribute data, please contact:
Jane Larkindale at jlarkindale@c-path.org or jane.larkindale@curefa.org.

Access the FA-ICD platform

The platform for FA-ICD is hosted by the Critical Path Institute Online Data Repository (CODR).

Request a Login           CODR Home Page

C-Path has a decade of experience in data standards development, platform development and hosting, patient-level data privacy stewardship, data platform security, and controlled access methodology.

C-Path currently provides secure hosting for data collected from more than 100 clinical trials, over 60,000 subjects, and nine different therapeutic areas, totaling more than 200 million data points.

Important information about FA-ICD content and access:

• The data platform contains, but is not limited to:
  • Demographic data
  • Friedreich’s Ataxia Rating Scale (FARS)
  • International Co-operative Ataxia Rating Scale (ICARS)
  • Activities of Daily Living Scale
  • Functional Disability Scale
  • 25-Foot Walk
  • 9-Hole Peg Test
  • Modified Fatigue Impact Scale (MFIS)
  • MOS Pain Effects Scale (PES)
  • Bladder Control Scale (BLCS)
  • Bowel Control Scale (BWCS)
  • Impact of Visual Impairment Scale (IVIS)
  • Sloane low contrast letter acuity scale. (LCLA)
  • SF-10 and SF-36
  • Vital signs
  • ECG
  • Echocardiogram
  • Genetic mutation
• C-Path has fully anonymized all data.
• Researchers must agree to the Terms and Conditions for Use of the FA-ICD data platform and submit an online application form to request access to the data platform.
• The FA-ICD Steering Committee approves data access for external users.
• The Resources tab within FA-ICD contains information to help users understand and make use of the platform capabilities.

Important information about data standardization:

• C-Path has normalized all data to the CDISC Study Data Tabulation Model (CDISC SDTM) to enable researchers to analyze the data in aggregate.
• FA-ICD provides basic information on how data are structured using CDISC. Knowledge of SDTM is required for effective use of the data. Information and training about SDTM are available through the CDISC website; researchers who receive access to FA-ICD will find a link to the CDISC website on the Resources tab.

A summary of detailed concepts captured by SDTM domains contained in the FA-ICD is provided in the table below.

* Note: The FARS is located in the FT domain because the answers to the questions are governed by the duration/number of times a patient could perform the task. The ICARS is located in the RS domain because the answers are more subjectively answered by the clinician/technician who is observing the patient performing the task.

FAQs on the FA-ICD database

Please click HERE to view Frequestly Asked Questions about the FA ICD Database.