Neurological

The longitudinal course of the symptoms in Friedreich’s ataxia

The researchers examined the progression of symptoms in patients with Friedreich’s ataxia during a prospective observational cohort study. Your results, published in the Lancet Neurology, can help support clinical trial designs and enable clinicians to better tailor therapies.

The study by the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) recruited patients at 11 university clinics, 5 in Germany and 1 clinic each in Austria, Belgium, France, Italy, Spain and Great Britain between 2010 and 2018, genetic tests and scales for assessing and evaluating Ataxia (SARA), Daily Living Activities (ADL), Inventory of Signs Without Ataxia (INAS), Spinocerebellar Ataxia Functional Index (SCAFI), and EQ-5D scores.

A total of 602 patients were enrolled at baseline, and 500 had 1-year, 465 2-year, 374 3-year, and 366 4-year follow-up dates. Most patients were homozygous for extended GAA repeats in the frataxin (FXN) gene and had typical disease (84%).

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Half of the patients (51%) were able to walk at baseline, and 51 patients lost walking ability during the follow-up visit.

The standardized SARA response mean increased from 0.32 points after one year to 0.90 points in the fourth year and the ADL from 0.35 to 1.05 points. These values ​​corresponded to an annual deterioration of 0.82 (standard error [SE], 0.05) points for SARA and 0.93 (SE, 0.05) points for ADL.

Stratified by outpatient status, patients who were outpatient had significantly higher SARA progression rates (1.12 vs. 0.50 points; time after group interaction, 0.62 points; P <0.0001). No significant difference was observed for ADL based on outpatient status.

The SCAFI scores developed at an annual rate of -0.05 (SE, 0.01) points. The progression of SCAFI was increased in outpatients with a significant time after group interaction (-0.04; SE, 0.01 points; P = 0.012). EQ-5D scores increased by -0.02 (SE, 0.003) points annually with a significant difference based on onset (0.02; SE, 0.01 points; P = 0.030) and a time after group interaction, in which the ambulatory status progressed more rapidly (0.02; SE, 0.006 points; P <0.0001). The INAS scores increased by 0.09 (SE, 0.02) points each year.

A breakpoint analysis showed that patients younger than 27 years of age at the start of the study had an increased annual SARA progression (1.31 vs. 0.56 points), as did patients with at least 347 GAA repetitions (1.25 vs. 0.99 points). The annual ADL progression was with disease onset before age 6 (1.44 vs. 0.88 points) and in patients who had lost the ability to walk before age 11 (1.45 vs. 0.89 points) connected.

This study was limited by its relatively low retention rates up to year 4.

These data have important implications that must be considered in the design of clinical trials investigating Friedreich’s ataxia. The study authors concluded that “ADL, with its ease of use and sensitivity to change, is well suited to be used as a functional primary endpoint for clinical trials in [Friedreich] Ataxia.”

Disclosure: This research was supported by Voyager Therapeutics. For a full list of the details, see the original article.

reference

K. Reetz, I. Dogan, RD. Hilgers et al .; EFACTS study group. History features of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study. Lancet Neurol. 2021; 20 (5): 362-372. doi: 10.1016 / S1474-4422 (21) 00027-2

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