Ketolysis is required for the proper development and function of the somatosensory nervous system

Enders J, Jack J, Thomas S, Lynch P, Lasnier S, Cao X, Swanson MT, Ryals JM, Thyfault JP, Puchalska P, Crawford PA, Wright DE. Ketolysis is required for the proper development and function of the somatosensory nervous system. Exp Neurol. 2023 Apr 24:114428. doi: 10.1016/j.expneurol.2023.114428. Epub ahead of print. PMID: 37100111. 

We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.

Natural History Studies Drive Data Sharing, Drug Approval

Heidt, A. (2023, May 1). Natural history studies drive data sharing, drug approval. Retrieved May 1, 2023, from BioSpace website: https://www.biospace.com/article/natural-history-studies-drive-data-sharing-drug-approval/ 

Two recent announcements—the world’s first treatment for Friedreich's ataxia (FA), whose approval was based in part on a natural history database, and a new data-sharing agreement between industry and nonprofit partners to investigate myopathy—underpin just how helpful these studies can be in establishing new collaborations to tackle rare diseases.

Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España

G. Ortega Suero, M.J. Abenza Abildúa, C. Serrano Munuera, I. Rouco Axpe, F.J. Arpa Gutiérrez, A.D. Adarmes Gómez, F.J. Rodríguez de Rivera, B. Quintans Castro, I. Posada Rodríguez, A. Vadillo Bermejo, Á. Domingo Santos, E. Blanco Vicente, I. Infante Ceberio, J. Pardo Fernández, E. Costa Arpín, C. Painous Martí, J.E. Muñoz, P. Mir Rivera, F. Montón Álvarez, L. Bataller Alberola, J. Gascón Bayarri, C. Casasnovas Pons, V. Vélez Santamaría, A. López de Munain, G. Fernández-Eulate, J. Gazulla Abío, I. Sanz Gallego, L. Rojas Bartolomé, Ó. Ayo Martín, T. Segura Martín, C. González Mingot, M. Baraldés Rovira, R. Sivera Mascaró, E. Cubo Delgado, A. Echavarría Íñiguez, F. Vázquez Sánchez, M. Bártulos Iglesias, M.T. Casadevall Codina, E.M. Martínez Fernández, C. Labandeira Guerra, B. Alemany Perna, A. Carvajal Hernández, C. Fernández Moreno, M. Palacín Larroy, N. Caballol Pons, A. Ávila Rivera, F.J. Navacerrada Barrero, R. Lobato Rodríguez, M.J. Sobrido Gómez, Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España (Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study), Neurología (English Edition), 2023, doi.org/:10.1016/j.nrleng.2023.04.003. 

 In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

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.