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Record W4406312640 · doi:10.1212/nxg.0000000000200236

Friedreich Ataxia

2025· article· de· W4406312640 on OpenAlexaffabout
Massimo Pandolfo

Bibliographic record

VenueNeurology Genetics · 2025
Typearticle
Languagede
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsMcGill University
Fundersnot available
KeywordsAtaxiaMedicinePhysical medicine and rehabilitationPsychiatry

Abstract

fetched live from OpenAlex

In the late 1800s, Nikolaus Friedreich first described “degenerative atrophy of the posterior columns of the spinal cord,” noting its connection to progressive ataxia, sensory loss, and muscle weakness, now recognized as Friedreich ataxia (FRDA). Renewed interest in the disease in the 1970s and 80s by the Quebec Cooperative Group and by Anita Harding led to the development of clinical diagnostic criteria and insights into associated biochemical abnormalities, although the primary defect remained unknown. In 1988, Susan Chamberlain mapped FRDA's location on chromosome 9. In the early 90s, collaborative research, including work by the author's team, identified a gene, later named FXN, containing an expanded GAA repeat—confirming it as the FRDA mutation. This discovery established a diagnostic foundation for FRDA, advancing genetic testing and opening new research avenues. These new areas of study included the characteristics, origin, and pathogenicity of the GAA repeat expansion; the characterization of frataxin, the encoded protein, including its subcellular localization, structure, and function; the identification of cellular pathways disrupted by frataxin deficiency; and the redefinition of FRDA phenotypes based on genetic testing, along with the study of FRDA's natural history. In addition, efforts focused on the search for biomarkers to reflect diagnosis, disease severity, and progression and, most importantly, the identification and development of therapeutic approaches in both preclinical and clinical settings. The creation of cellular and animal models was crucial to this progress, as was the formation of consortia to collaboratively drive basic and clinical research forward. Now, 28 years after the gene discovery, although much remains to be understood about the disease's mechanisms and the development of effective therapies, the progress is undeniable. A thriving community has emerged, uniting researchers, health care providers, industry professionals, individuals with FRDA, their families, and dedicated volunteers. With this collective effort, a cure is within reach.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.040
Threshold uncertainty score0.135

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0020.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.002
Science and technology studies0.0020.001
Scholarly communication0.0030.002
Open science0.0010.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0400.044

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.284
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes2
Has abstractyes

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