The European Friedreich Ataxia Consortium for Translational Studies (EFACTS) group suggested specific outcome measures it found to be best suited to clinical trials testing possible treatments for Friedreich’s ataxia, and emphasized that studies looking at disease-modifying therapies need to run for at least two years.
Jörg Schulz, a neurologist at RWTH Aachen University Hospital in Aachen, Germany, led the oral presentation titled “Natural history of Friedreich ataxia” that aims to improve such trials. He spoke on behalf of the EFACTS study group at the International Ataxia Research Conference (IARC) on Thursday. IARC 2017 concludes in Pisa, Italy, on Sept. 30.
Friedreich’s ataxia is caused by genetic mutations in the frataxin gene; specifically, an abnormal repeat of a GAA sequence diminishes production of the frataxin protein in cells — a protein that’s a vital component of a cell’s energy-producing organelles called mitochondria.
The disease is characterized by a progressive degeneration of the nervous system and difficulties with movement. Symptoms can first become evident during childhood or adolescence, or in early adulthood.
Increased interest and investment in Friedreich’s ataxia has led to researchers uncovering some mechanisms underlying the disease, a key achievement for the next step — developing targeted therapies that might stop disease progression and modify its course.
“To design such studies knowledge of the natural history of the disease, identification of scales and biomarkers which capture the progression of the disease is of uttermost importance,” the researchers wrote.
EFACTS set up a registry to better understand the natural history Friedreich’s ataxia, natural history being the course of a disease over time — from onset to resolution — in a person.
“Natural history data are pivotal for the design and conduct of interventional studies, and are of particular importance for interventional studies with the aim of disease modification,” Schulz said in his presentation.
According to the researcher, patient registries are the “golden standard” to achieve this.
The first article showed that “earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression,” and that the Scale for the Assessment and Rating of Ataxia (SARA) “might be the most suitable measure to monitor disease progression” in clinical trials.
The second study confirmed that younger age at disease onset is a major predictor of faster disease progression, and that SARA is again “a suitable clinical rating scale to detect deterioration of ataxia symptoms over time.” The study also showed that the activities of daily living (ADL) assessment scale “is an appropriate measure to monitor changes in daily self-care activities.”
Determining outcome measures best suited for studies in a particular disease are crucial to designing clinical trials for patients.
Data from the EFACTS registry, overall, showed that SARA and ADL scales monitor disease with high sensitivity in Friedreich’s ataxia patients.
They also validated previous reports showing that larger numbers of GAA repeats are linked to earlier disease onset.
The results also underscored “that FRDA [Friedreich’s ataxia] shows slower progression than reported from retrospective data.” This, the researchers concluded, “imply that a study duration of at least 2 years is necessary in interventional studies aiming at disease modification without a direct symptomatic effect of the drug.”
Taken together, this study could help in the design of trials better tailored to Friedreich’s ataxia patients with greater chances of advancing potential treatments.