Frataxin analysis using triple quadrupole mass spectrometry: application to a large heterogeneous clinical cohort

Lynch, D.R., Rojsajjakul, T., Subramony, S.H. et al. Frataxin analysis using triple quadrupole mass spectrometry: application to a large heterogeneous clinical cohort. J Neurol (2023). doi:10.1007/s00415-023-12118-x 

The present data show that assay of FXN-M and FXN-E levels in blood provides an appropriate biofluid for assessing their repletion in particular clinical contexts.

Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey

Morris, S., Vallortigara, J., Greenfield, J. et al. Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey. Orphanet J Rare Dis 18, 382 (2023). doi:10.1186/s13023-023-02971-4 

Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.

Human frataxin, the Friedreich ataxia deficient protein, interacts with mitochondrial respiratory chain

Davide D, Federica C, Marco B, Elisa B, Silvia M, Giulia T, Federica D, Ottaviani D, Elena M, Luigi L, Elisa G, Elena Z, Antonella R, Milena B, Geppo S, Donatella C, Leonardo S, Paola C. Human frataxin, the Friedreich ataxia deficient protein, interacts with mitochondrial respiratory chain. Cell Death Dis. 2023 Dec 8;14(12):805. doi: 10.1038/s41419-023-06320-y. PMID: 38062036. 

Using healthy cells and different FRDA cellular models we found that frataxin interacts with these three respiratory complexes. Furthermore, by EPR spectroscopy, we observed that in mitochondria from FRDA patients' cells the decreased level of frataxin specifically affects the FeS cluster content of complex I. Remarkably, we also found that the frataxin-like protein Nqo15 from T. thermophilus complex I ameliorates the mitochondrial respiratory phenotype when expressed in FRDA patient's cells.

Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia

Magnus Johnsson, Henrik Zetterberg, Kaj Blennow, Christopher Lindberg, Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia, Heliyon, 2023, e23347, ISSN 2405-8440, doi:10.1016/j.heliyon.2023.e23347. 

(Last) Magnus Johnsson, Henrik Zetterberg, Kaj Blennow, Christopher Lindberg, Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia, Heliyon, Volume 10, Issue 1, 2024, e23347, ISSN 2405-8440, doi.:10.1016/j.heliyon.2023.e23347.

FRDA is less prevalent in our region of Sweden than could be assumed. In concordance with previous studies from other authors, we find that p-NfL may be increased in patients with FRDA, but less so in older more clinically affected patients. Thus, we conclude that on an individual basis, p-NFL is of uncertain clinical value as a suitable biomarker.

Intensive Multimodal Treatment for A Young Adult with Friedreich Ataxia: A Case Report

Grace Battal, Nicolas Pinsault, Berthe Hanna-Boutros. Intensive Multimodal Treatment for A Young Adult with Friedreich Ataxia: A Case Report. International Journal of Physiotherapy and Research, 2023, 11 (3), pp.4508-4516. 10.16965/ijpr.2023.110 . hal-04134585 

 The FRDA patient displayed improvement in all outcome measures. Strength, ataxia severity and functional abilities were enhanced while a higher level of independence was gained. Our observations suggest that an intensive multimodal approach holds potential in the management of FRDA and call for further research.

A modified mouse model of Friedreich's ataxia with conditional Fxn allele homozygosity delays onset of cardiomyopathy

A modified mouse model of Friedreich's ataxia with conditional Fxn allele homozygosity delays onset of cardiomyopathy; Tyler L Perfitt, Claudia Huichalaf, Renea Gooch, Anna Kuperman, Youngwook Ahn, Xian Chen, Soumya Ullas, Dinesh Hirenallur-Shanthappa, Yutian Zhan, Diana Otis, Laurence O. Whiteley, Christine Bulawa, and Alain Martelli, American Journal of Physiology-Heart and Circulatory Physiology 0 0:0, doi:10.1152/ajpheart.00496.2023 

This modified model reproduced important pathophysiological and biochemical features of FA over a longer timescale than previous cardiac-specific mouse models, offering a larger window for studying potential therapeutics.

Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?

Aguilera, C., Esteve-Garcia, A., Casasnovas, C. et al. Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?. BMC Med Genomics 16, 312 (2023). doi:10.1186/s12920-023-01743-0 

We describe a patient presenting with novel intragenic deletion and an expansion on the FXN gene who shows the typical progression and clinical features of FRDA. We believe that parental sample testing should be performed in all FRDA patients that present an apparent biallelic expansion in order to offer proper genetic counselling.

Health-Related Quality of Life in Patients with Inherited Ataxia in Ireland

Menon, P.J., Yi, T.X., Moran, S. et al. Health-Related Quality of Life in Patients with Inherited Ataxia in Ireland. Cerebellum (2023). doi:10.1007/s12311-023-01640-3 

 This study is the first cross-sectional study on HRQoL in patients with inherited ataxia in Ireland. It highlights high rates of unemployment, difficulty with daily activities and physical functioning limitations, which is worse than comparative international studies. Given the limited therapeutic options currently available, optimising HRQoL is an important aspect of managing ataxia.

Loss of homeostatic functions in microglia from a murine model of Friedreich's ataxia

Ilaria Della Valle, Martina Milani, Simona Rossi, Riccardo Turchi, Flavia Tortolici, Valentina Nesci, Alberto Ferri, Cristiana Valle, Daniele Lettieri-Barbato, Katia Aquilano, Mauro Cozzolino, Savina Apolloni, Nadia D'Ambrosi, Loss of homeostatic functions in microglia from a murine model of Friedreich's ataxia, Genes & Diseases, 2023, 101178, doi:10.1016/j.gendis.2023.101178. 

 Although several reports correlated microglia morphology to cerebellar degeneration in FRDA in vivo, this work is the first to provide multilayer evidence (phenomics, transcriptomics, and metabolic analysis) that FRDA microglia are dysfunctional, suggesting a contribution of non-cell autonomous mechanisms in FRDA pathogenesis.

Effectiveness of rehabilitation intervention in persons with Friedreich ataxia

Paparella G, Stragà C, Vavla M, Pesenti N, Merotto V, Martorel GA, Zalunardo S, Armellin M, Comiotto J and Martinuzzi A (2023) Effectiveness of rehabilitation intervention in persons with Friedreich ataxia. Front. Neurol. 14:1270296. doi: 10.3389/fneur.2023.1270296 

 We report that the IR significantly improves motor performance and ataxia symptoms in patients with FRDA. Our study shows significant functional improvement in all the outcome measures used, except for NHPT bilaterally. FARS and SARA scores post-IR are significatively reduced when compared (p < 0.001).