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).

The Cardiac Calcium Handling Machinery is Remodeled in Friedreich's Ataxia

The Cardiac Calcium Handling Machinery is Remodeled in Friedreich's Ataxia, Roman Czornobil, Obada Abou- Assali, Elizabeth Remily- Wood, David R Lynch, Sami F. Noujaim, Bojjibabu Chidipi bioRxiv 2023.11.09.566141; doi:10.1101/2023.11.09.566141 

Conclusion: The development of left ventricular contractile dysfunction in FA is associated with reduced expression of calcium handling proteins and mitochondrial dysfunction.

Aspectos médico-legales del consentimiento en la nueva regulación de la eutanasia. A propósito de un caso

Fernández Resina, Laura, Repositorio Institucional UIB, Treballs dels estudiants, TFG, Facultat de Medicina, Grau en Medicina (GMED). Fecha: 2023 Fecha de depósito: 2023-11-13. 

 El propósito del presente trabajo es analizar el caso de un paciente postadolescente afectado de ataxia de Friedreich que plantea su deseo de morir para estudiar los aspectos relativos a su consentimiento en relación a la eutanasia.

Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives

Hushpulian DM, Kaidery NA, Dutta D, Sharma SM, Gazaryan I, Thomas B. Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives. Bioessays. 2023 Nov 2:e2300176. doi: 10.1002/bies.202300176. Epub ahead of print. PMID: 37919861. 

FDA-approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non-specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1.

Ataxia de Friedreich, revisión y actualización de la literatura con búsqueda sistemática de casos en Latinoamérica

Alfaro-Olivera, María, Calle-Nuñez, Adriana, Uribe-León, Alfonso, Araujo-Aliaga, Ismael, Aguirre-Quispe, Wilfor, Sarapura-Castro, Elison, & Cornejo-Olivas, Mario. (2023). Ataxia de Friedreich, revisión y actualización de la literatura con búsqueda sistemática de casos en Latinoamérica. Revista de Neuro-Psiquiatría, 86(1), 45-61. Epub 27 de abril de 2023. doi:10.20453/rnp.v86i1.4466 

En esta revisión, se actualizan aspectos epidemiológicos, fisiopatológicos y clínico-terapéuticos y se conduce una búsqueda sistemática de casos de AF reportados en Latinoamérica. La prevalencia de AF en poblaciones caucásicas es estimada entre 2 y 5 casos por 100 000 habitantes. En Latinoamérica se han publicado 35 estudios que reúnen 1481 casos en 6 países.

Thermodynamic Stabilization of Human Frataxin

Thermodynamic Stabilization of Human Frataxin. Reyes Núñez-Franco, Angel Torres-Mozas, Claudio D. Navo, Andreas Schedlbauer, Mikel Azkargorta, Ibon Iloro, Félix Elortza, Gabriel Ortega, Oscar Millet, Francesca Peccati, Gonzalo Jiménez-Osés. bioRxiv 2023.09.08.556816; doi:10.1101/2023.09.08.556816

This case-study highlights the power of our combined computational approach to generate optimized variants, adequate for protein-based therapeutics.

Evaluation of diaphragm functions with diaphragm ultrasound and Evaluation of diaphragm functions with diaphragm ultrasound and pulmonary function tests in individuals with Friedreich?s ataxia pulmonary function tests in individuals with Friedreich?s a

Yetkin, N. A., Yetkin, M. F., Baran Ketencioğlu, B., Oymak, F. S., Gülmez, İ., Yılmaz, İ., ... Tutar, N.(2023). Evaluation of diaphragm functions with diaphragm ultrasound and Evaluation of diaphragm functions with diaphragm ultrasound and pulmonary function tests in individuals with Friedreich?s ataxia pulmonary function tests in individuals with Friedreich?s a. TURKISH JOURNAL OF MEDICAL SCIENCES , vol.53, no.5, 1301-1311. Doi:10.55730/1300-0144.5696 

 Conclusion: Diaphragm ultrasound may reveal respiratory dysfunction better than PFT. Diaphragm excursion and TF are associated with disease scores in individuals with FDRA. Further studies are needed regarding the detection of alveolar hypoventilation.

Free-Water Imaging in Friedreich Ataxia Using Multi-Compartment Models

Fernandez, L., Corben, L.A., Bilal, H., Delatycki, M.B., Egan, G.F. and Harding, I.H. (2023), Free-Water Imaging in Friedreich Ataxia Using Multi-Compartment Models. Mov Disord. doi:10.1002/mds.29648  

This study supports further applications of multi-compartment diffusion modeling, and investigations of free-water as a measure of disease expression and progression in FRDA

Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions

Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions; Ashraf Mohammed, M. Brett Waddell, Ieva Sutkeviciute, Adithi Danda, Steven J. Philips, Walter Lang, P. Jake Slavish, Sandra J. Kietlinska, Mangesh Kaulage, Das Sourav, and Aseem Z. Ansari; J. Am. Chem. Soc. 2023, XXXX, XXX, XXX-XXX; Publication Date:November 3, 2023; doi:10.1021/jacs.3c06297 

SynTEF1, a prototype synthetic genome reader/regulator (SynGR), was designed to target GAA triplet repeats and restore the expression of frataxin (FXN) in Friedreich’s ataxia patients. 

SynGRs as chemical probes provide unique insights into the molecular recognition principles utilized by natural factors to precisely regulate gene expression, and they guide the design of more sophisticated synthetic gene regulators with greater therapeutic potential.