Leveraging Real-World Data to Define Clinical Milestones and Assess Pharmacologic Impact in Friedreich’s Ataxia Progression

Friedreich’s ataxia (FA) is a progressive disease that affects the nervous system, the heart and other organs, but it progresses differently in each person. This variability makes it difficult to design clinical trials and measure treatment success. Most clinical trials in FA have used a rating scale called the modified Friedreich’s Ataxia Rating Scale (mFARS) to track disease progression, but this scale may not reflect meaningful changes in patients’ everyday lives. To improve this, Dr Venuto proposes tracking major health “milestones” like wheelchair use, heart disease diagnosis, or serious falls—events that matter to patients and doctors. Using a large database of electronic health records (EHRs) from over 1,200 people with FA, he will define and study milestones across six important areas of health: mobility, heart health, diseases like diabetes, mental health, sensory function (like vision and hearing), and serious healthcare events such as hospitalization. Dr Venuto will explore how often these milestones occur, how they relate to disease onset, and whether combining milestones offers a better way to measure progression. He will also simulate how these composite milestones could be used as outcomes in future clinical trials, including how many participants and how much time would be needed to detect a treatment effect. Finally, he will explore whether any medications, including those not currently approved for FA, affect milestone progression, potentially uncovering new treatment options. The goal is to create better tools for tracking FA progression, improve clinical trial design, and accelerate the development of effective therapies.