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Review
. 2025 May 22:16:1558493.
doi: 10.3389/fneur.2025.1558493. eCollection 2025.

Clinical and cognitive assessment in Friedreich ataxia clinical trials: a review

Álvaro Darriba  1 , Arnold Munnich  2 , Pedro Cardoso-Leite  3 , Benoît Funalot  4   5   6 , Florian Waszak  1
Affiliations
Review

Clinical and cognitive assessment in Friedreich ataxia clinical trials: a review

Álvaro Darriba et al. Front Neurol. .

Abstract

Friedreich ataxia (FRDA) is the most common type of inherited ataxia. It is a neurodegenerative disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, and reduced proprioception and vibration sensation. Although a number of clinical trials have been conducted, there is currently no cure for this disease. In this article we review those clinical trials with a focus on the instruments used as endpoints to assess clinical progression, and discuss the potential benefits of integrating additional measures, including assessments from overlooked domains. We also review tools used to evaluate cognitive functions in individuals with FRDA, particularly those employing quantitative, objective, and time-based measures. We argue for the inclusion of cognitive and speech-related assessments in clinical trials, and examine the potential of developments in cognitive neuroscience and technology to address current measurement challenges and support more accurate and comprehensive evaluation of treatment effects. These innovations have the potential to complement existing approaches, enhance trial design, and advance clinical care.

Keywords: Friedreich’s ataxia; behavioral assessment; clinical trials; cognitive assessment; outcome measures.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
(A) Number of studies employing instruments dedicated to the assessment of the general cognitive state, intelligence, and a series of cognitive dimensions. (B) Percentage of studies reporting significant results among those evaluating each particular dimension.
Figure 2
Figure 2
Flowchart representing the use of precise time measures and computerized methods in studies on cognition in FRDA patients.
Figure 3
Figure 3
(A) Number of studies using each type of endpoint. (B) Number of studies using each of the different clinical rating scales. (C) Number of studies using each of the timed performance measures. (D) Number of studies using each of the different ADL/Patient report scales (LCLA, Low Contrast Letter Accuity; EQ-5D, EuroQol 5-Dimension; FAIS, Friedreich Ataxia Impact Scale; MFIS, Modified Fatigue Impact Scale; PGI-C, Patient Global Impression of Change; SF-36, Short Form-36 Health Survey).
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