Short-read genome sequencing allows ‘en route’ diagnosis of patients with atypical Friedreich ataxia

Fleszar, Z., Dufke, C., Sturm, M. et al. Short-read genome sequencing allows ‘en route’ diagnosis of patients with atypical Friedreich ataxia. J Neurol (2023). doi:10.1007/s00415-023-11745-8 

We here showcase how the introduction of short-read genome sequencing (SR-GS) allows to overcome these biases in the work-up of complex ataxias, as it allows to detect even intronic STRs (i) “en route”, i.e. with detection not requiring any primary direct gene analysis; and (ii) in a phenotype-independent fashion”, i.e. also for those atypical phenotypic presentations where the corresponding gene and mutational mechanism had not been part of the prior differential clinical diagnosis.

Communicating Health Literacy on Prescription Medications on Social Media: In-depth Interviews With “Patient Influencers”

Willis E, Friedel K, Heisten M, Pickett M, Bhowmick A; Communicating Health Literacy on Prescription Medications on Social Media: In-depth Interviews With “Patient Influencers”, J Med Internet Res 2023;25:e41867, URL: https://www.jmir.org/2023/1/e41867, DOI: 10.2196/41867 

This study aimed to explore how patient influencers communicate health literacy on pharmaceutical medications on social media to their communities of followers.

Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich’s Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress

Lew, S.Y.; Mohd Hisam, N.S.; Phang, M.W.L.; Syed Abdul Rahman, S.N.; Poh, R.Y.Y.; Lim, S.H.; Kamaruzzaman, M.A.; Chau, S.C.; Tsui, K.C.; Lim, L.W.; Wong, K.H. Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich’s Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress. Biology 2023, 12, 559. doi:10.3390/biology12040559 

 Our study demonstrated that adenosine targeted mitochondrial defects in FRDA, contributing to improved mitochondrial function and biogenesis, leading to cellular iron homeostasis. Therefore, we suggest a possible therapeutic role for adenosine in FRDA.

Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players

Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players. Schiavi, Alfonso et al., iScience, Volume 26, Issue 4, 106448. doi:10.1016/j.isci.2023.106448 

 

We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation.

Establishing efficacy based on single-arm trials submitted as pivotal evidence in a marketing authorisation - Scientific guideline

First published: 21/04/2023, Consultation dates: 21/04/2023 to 30/09/2023; EMA/CHMP/564424/2021

This reflection paper is intended to reflect the current thinking of EMA's Committee for Medicinal Products for Human Use (CHMP) on single-arm trials (SATs) that are submitted as pivotal evidence for establishing efficacy in a marketing authorisation application. The reflection paper discusses considerations in relation to the design, planning, conduct, analysis and interpretation of results derived from single-arm trials. It is applicable across different therapeutic areas, including for rare diseases.

The role of HDAC3 and its inhibitors in regulation of oxidative stress and chronic diseases

He, R., Liu, B., Geng, B. et al. The role of HDAC3 and its inhibitors in regulation of oxidative stress and chronic diseases. Cell Death Discov. 9, 131 (2023). doi:10.1038/s41420-023-01399-w 

 In this review, we comprehensively summarize the knowledge of the relationship of HDAC3 with mitochondria function and metabolism, ROS-produced enzymes, antioxidant enzymes, and oxidative stress-associated transcription factors. We also discuss the role of HDAC3 and its inhibitors in some chronic cardiovascular, kidney, and neurodegenerative diseases.

Auditory neuropathy in mice and humans with Friedreich ataxia

Rance, G., Carew, P., Winata, L., Sale, P., Delatycki, M. and Sly, D. (2023), Auditory neuropathy in mice and humans with Friedreich ataxia. Ann Clin Transl Neurol. https://doi.org/10.1002/acn3.51777 

This study found degenerative changes in auditory structure and function in YG8Pook/J mice, indicating that auditory measures in these animals may provide a model for testing Friedreich ataxia treatments. In addition, auditory steady-state response findings in a clinical population suggested that these scalp-recorded potentials may serve as an objective biomarker for disease progress in affected individuals.

Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a mouse model of Friedreich's ataxia

TURCHI R, SCIARRETTA F, TIBERI M, et al. Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a mouse model of Friedreich's ataxia. bioRxiv; 2023. DOI: 10.1101/2023.04.06.535845. 

In conclusion, this study identified vWAT as an important player in the onset of metabolic complications typical of FA and suggests butyrate as safe and promising adjuvant tool to treat metabolic complications in FA.

Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich’s Ataxia

Elisabetta Indelicato, Alexander Kirchmair, Matthias Amprosi, Stephan Steixner, Wolfgang Nachbauer, Andreas Eigentler, Nico Wahl, Galina Apostolova, Anne Krogsdam, Rainer Schneider, Julia Wanschitz, Zlatko Trajanoski, Sylvia Boesch, Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich’s Ataxia, Human Molecular Genetics, 2023;, ddad051, doi:10.1093/hmg/ddad051 

 Our findings reflect a double hit in the pathophysiology of FRDA: a transcriptional/translational issue, and a profound mitochondrial failure downstream. Leptin upregulation in the skeletal muscle in FRDA may represent a compensatory mechanism of mitochondrial dysfunction, which is amenable to pharmacological boosting. Skeletal muscle transcriptomics is a valuable biomarker to monitor therapeutic interventions in FRDA.

Efficiency of a 3-week multicomponent rehabilitation on improving the function in a patient with Friedreich's ataxia: A case report

Samardžić Vesna; Vojnosanitetski pregled 2023, vol. 80, iss. 2, pp. 182-187. DOI:10.2298/VSP220209027S 

We present a 26-year-old female with FA who had severe truncal and limb ataxia, speech difficulty, and poor walking ability. During the three-week rehabilitation, an individually tailored physical therapy program based on PNF stabilization techniques was applied. The implemented rehabilitation program resulted in an overall functional improvement. The reduction in ataxia was registered according to the Scale for the Assessment and Rating of Ataxia (SARA). The Functional Independence Measure (FIM) instrument - a component of locomotion, revealed greater independence in walking. Conclusion. A rehabilitation program based on PNF stabilization techniques may reduce ataxia and improve walking ability in patients with FA.