Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies

Santos C, Malheiro S, Correia M, Damásio J. Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies. Cells. 2023; 12(7):1037. https://doi.org/10.3390/cells12071037 

In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed. Conclusion: The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype in vivo. Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.

Traitement somatosensoriel proprioceptif et tactile chez les personnes atteintes d’ataxie de Friedreich, une étude d’imagerie par résonance magnétique fonctionnelle

Virginie Destrebecq, Valérie Martinet, Antonin Rovai, Nicolas Trotta, Gilles Naeije, Traitement somatosensoriel proprioceptif et tactile chez les personnes atteintes d’ataxie de Friedreich, une étude d’imagerie par résonance magnétique fonctionnelle, Volume 8063, Issue 100, 04/2023, Pages S1-S210, ISSN 0035-3787, doi: 10.1016/j.neurol.2023.01.629 

Discussion Ces paradigmes d’IRMf capturent la dichotomie entre les déficiences tactiles et proprioceptives chez les personnes atteintes de FRDA. L’altération proprioceptive prédominante rappelle le patron lié au vieillissement. Conclusion L’âge et la FRDA pourraient se potentialiser et rendre les déficits de perception tactile cliniquement pertinents.

Clinically meaningful metrics of speech in neurodegenerative disease: Quantification of speech intelligibility and naturalness in ataxia

Clinically meaningful metrics of speech in neurodegenerative disease: Quantification of speech intelligibility and naturalness in ataxia Adam P Vogel, Paul Maruff, Hannah Reece, Hannah Carter, Geneieve Tai, Benjamin G Schultz, Louise Corben, Martin B Delatycki, Athanasios Tsanas; medRxiv 2023.03.28.23287878; doi:10.1101/2023.03.28.23287878

We demonstrate a subset of measures are strongly associated with all four clinical scales. Objective speech data replicated expert assessments of naturalness and intelligibility. These scores represent a lower level of variability than observed between subjective listener ratings. Findings provide evidence there are specific objective markers of speech that change over time and reflect clinical aspects of the disease. Discussion: The use of a large dataset yielded a speech assay capable of accurately approximating expert listener ratings of key clinical aspects of dysarthria severity. Distinct but complementary subsets align with disease severity and speech related quality of life.

Sequencing through hyperexpanded Friedreich’s ataxia-GAA repeats by nanopore technology: implications in genotype–phenotype correlation

Bharathram Uppili, Pooja Sharma, Istaq Ahmad, Shweta Sahni, Vivekanand Asokachandran, Anil B Nagaraja, Achal K Srivastava, Mohammed Faruq, Sequencing through hyperexpanded Friedreich’s ataxia-GAA repeats by nanopore technology: implications in genotype–phenotype correlation, Brain Communications, Volume 5, Issue 2, 2023, fcad020, doi:10.1093/braincomms/fcad020

The total throughput achievable through our protocol can allow for screening of up to 96 samples per flow cell in less than 24 h. The proposed method is clinically scalable and deployable for day-to-day diagnostics. In this paper, we demonstrate to resolve the genotype–phenotype correlation of Friedreich’s ataxia patients with better accuracy.