Researchers report that the analysis of the neurological changes occurring in patients with Friedrich’s Ataxia (FDRA) may serve as prediction factors of disease progression and be useful in the design of clinical trials to investigate future therapies. The findings suggest, namely, that clinical trials would benefit from recruitment of younger patients.
The study, “Progression Of Friedreich Ataxia: Quantitative Characterization Over 5 Years,” by Maya Patel, MD, from the Children’s Hospital of Philadelphia, and her colleagues was published in the journal Annals of Clinical and Translational Neurology.
To date, there is no approved treatment for FRDA, which may be greatly due to the failure of drugs tested in inadequately conceived clinical trials. This led researchers to hypothesize whether the analysis of the neurological outcomes and changes presented in FDRA patients over time could lead to the identification of factors that could help predict disease progression. The identification of such factors can contribute relevantly to the proper design of clinical trials with FDRA patients.
Researchers evaluated 812 patients from 12 U.S. sites to investigate factors such as age, gender and genetic severity, particularly the length of GAA repeats, which are the genetic anomalies that affect the frataxin gene, leading to FDRA.
The scientists evaluated whether these factors would predict the outcome in several tests, namely the Friedreich Ataxia Rating Scale (FARS, a neurological exam with several components), a modified version of FARS (involving direct patient participation), the Ataxia Staging test, the 9‐Hole Peg Test and the Timed 25‐Foot Walk (tests for general disability), the Contrast Letter Acuity (a visual acuity test) and self‐reported surveys on the activities of daily living. These tests were repeated in patients who returned after five years.
Results indicated that, across patients from different institutions, younger age predicted a faster disease progression and a worse outcome in the above-mentioned tests. However, over time, the best predictor of progression was genetic severity. It was not easy to separate the contribution of each factor, which means more studies are needed to validate them as predictors of disease progression, researchers said.
“As it is difficult to fully separate the confounding effects of subject age and GAA repeat length, our data are most useful when viewed from the perspective of [GAA repeats] being the most important biological variable modulating progression, and subject age being the most readily identified practical variable affecting speed changes,” the authors wrote in their report. “Such guidelines can be used as practical criteria for stratification of clinical trials.”
Several limitations interfere with the development of studies on FDRA, namely a decrease in the number of patients due to disease progression, the rarity of patients and limited financial resources. These limitations contributed to the low rate of return of patients after the five-year period of this study, which hinders long-term analysis. However, according to the authors, the demographic characteristics of the group of patients analyzed did not change much over time, supporting that the findings are unlikely to represent selection bias.