The UNIFAI Natural History Study of Friedreich’s Ataxia (FA) represents a significant global effort to understand the progression of this rare, inherited, multi-system condition characterized by progressive neurological and cardiac symptoms. Caused by mutations in the FXN (frataxin) gene, FA presents a complex challenge to researchers and clinicians alike.
This prospective, longitudinal, observational study is designed to capture data from study visits conducted over time, following a single protocol across all sites. Participants with FA from around the world will be assessed annually for up to 25 years. The study involves yearly visits where data is collected from medical records, medical history, and clinical outcome assessments. These assessments include neurological exams, timed walking tests, upper limb function measures, and patient-reported quality of life assessments. Additionally, sites have the option to collect further data related to speech, vision, fatigue, balance, and cognition.
The UNIFAI study harmonizes two well-established, long-standing natural history studies in FA: FACOMS (conducted in the US, Canada, Australia, New Zealand, and India) and EFACTS (conducted in European countries). By uniting these studies, researchers aim to leverage the power of previously collected data and expand the network of clinical research centers specializing in FA, known as the FA-Global Clinical Consortium.
With the recent advances in understanding the genetic and cellular dysfunction of FA, there has been significant growth in the discovery and development of therapeutic approaches. The UNIFAI study seeks to build upon this momentum by focusing on several key objectives, including assessing the natural history of FA by collecting data from diagnosed individuals of all ages and stages of disease progression. This data encompasses demographics, medical history, medications, neurological and functional assessments, cardiac examinations, laboratory studies, and health questionnaires.
The study aims to evaluate clinical outcomes in individuals with FA, such as disease progression, symptom severity, and overall quality of life, by examining various influencing factors. These factors include genetic mutation, demographics (age, geography), co-existing conditions, medications, or treatments. By tracking outcomes over time, researchers hope to identify patterns, trends, and potential variations in subgroups or in the effectiveness of therapies or interventions across a diverse group of participants.
Moreover, the UNIFAI study will play a crucial role in identifying clinical milestones and changes in natural history over time as new treatments emerge. It will monitor how these interventions alter the disease's trajectory, potentially leading to the identification of crucial tipping points, disease landmarks, or stages where interventions can be most impactful. This study has the potential to significantly improve our understanding of FA and lead to more effective treatments and improved outcomes for those living with FA.
In addition to informing clinical trial design, the UNIFAI study aims to develop and validate novel clinical outcome assessments and biomarkers that can be used in clinical trials. By capturing data from a wide and diverse cohort of individuals with FA, the study will inform the selection of inclusion and exclusion criteria and power calculations for trial designs with specific clinical outcome measures.
Key inclusion criteria for the study include both males and females of any age with a genetically confirmed diagnosis of Friedreich ataxia, who provide written informed consent. For underage participants, both the participant and their parent or legally authorized representative must sign the informed consent form. Exclusion criteria include the inability or unwillingness to provide informed consent, acute or ongoing medical or other conditions that would interfere with the study's conduct and assessments, and any reason, in the opinion of the investigator, that the participant would be unlikely or unable to comply with study protocol requirements.
