Remember friedreich ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy: revisited

Anwar BABAN, Marianna CICENIA, Lorena TRAVAGLINI, Federica CALÍ, Gessica VASCO, Paola FRANCALANCI, Antonio NOVELLI, Rachele ADORISIO, Antonio AMODEO, Bruno DALLAPICCOLA, Enrico BERTINI, Fabrizio DRAGO. Minerva Pediatr 2021 Apr 02. DOI: 10.23736/S2724-5276.21.05969-3 

We believe on the importance of taking in consideration this rare condition even in a toddler with apparently isolated cardiomyopathy and especially when conventional investigations give negative results. We discuss potential trigger effect of heart transplant as a precipitating factor in manifesting neurological symptoms. This observation corresponds to our experience and relates to three patients described so far (the third patient died suddenly). Early onset cardiomyopathy with FRDA should increase awareness of this rare condition and we highlight HT successful outcome. Further reports are needed to delineate this rare condition in youngsters.

The Cardioprotective Mechanism of Phenylaminoethyl Selenides (PAESe) Against Doxorubicin-Induced Cardiotoxicity Involves Frataxin

Fu Xiaoyu, Eggert Mathew, Yoo Sieun, Patel Nikhil, Zhong Juming, Steinke Ian, Govindarajulu Manoj, Turumtay Emine Akyuz, Mouli Shravanthi, Panizzi Peter, Beyers Ronald, Denney Thomas, Arnold Robert, Amin Rajesh H.; Front. Pharmacol., 12 April 2021 doi:10.3389/fphar.2020.574656

Mechanistically, we demonstrated that DOX impedes the stability of the iron-sulfur cluster biogenesis protein Frataxin (FXN) (0.5 fold), resulting in enhanced mitochondrial free iron accumulation (2.5 fold) and reduced aconitase activity (0.4 fold). Our findings further indicate that PAESe prevented the reduction of FXN levels and the ensuing elevation of mitochondrial free iron levels.

Diseases Costs and Impact of the Caring Role on Informal Carers of Children with Neuromuscular Disease

Rodríguez, A.A.; Martínez, Ó.; Amayra, I.; López-Paz, J.F.; Al-Rashaida, M.; Lázaro, E.; Caballero, P.; Pérez, M.; Berrocoso, S.; García, M.; Luna, P.M.; Pérez-Núñez, P.; Passi, N.. International Journal of Environmental Research and Public Health. 2021 Mar;18(6). DOI: 10.3390/ijerph18062991. 

This study shows that carers of children with NMDs have to face a number of high costs related to their own physical and psychological health. Women represented the majority percentage of participants, and most of them had severely dependent children. Therefore, it was perceived that both the group of children with severe support needs, as well as their carers, had greater needs. In turn, it is important to note that there is some public funding for those affected to ensure that they can have access to health services. However, funding from regional governments and non-profit organizations is virtually non-existent for expenses associated with professional support for carers. Moreover, if these carers start from a low socioeconomic situation, dedicating themselves to caregiving increases their vulnerability. Therefore, these situations give rise to social inequality in this group. Finally, our study also found that carers who are female, single or separated and unemployed showed worse physical and psychological health.

A Phase 2a investigator-initiated open-label clinical trial assessing elamipretide

BOSTON, April 6, 2021 /PRNewswire/ -- Stealth BioTherapeutics Corp (Nasdaq: MITO), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today reported financial results for the year ended December 31, 2020 and announced recent business highlights. 

Expansion of cardiomyopathy franchise: A Phase 2a investigator-initiated open-label clinical trial assessing elamipretide in a cohort of patients affected by visual decline and/or cardiomyopathy associated with Friedreich's ataxia is expected to commence during Q2 2021.

Healx launches partnership with Ataxia UK and FARA to find treatments for rare neurodegenerative condition

Cambridge UK – 7 April 2021 – Healx, the AI-powered, patient-inspired technology company accelerating the discovery and development of rare disease treatments at scale, is excited to announce its latest patient group partnerships. Working in collaboration with Ataxia UK and FARA, Healx will leverage its state-of-the-art AI platform and drug discovery expertise to develop novel treatments for Friedreich’s ataxia – a rare neurodegenerative condition that causes issues with balance, speech and coordination.

Biochemical alterations precede neurobehavioral deficits in a novel mouse model of Friedreich ataxia

Marta Medina-Carbonero, Arabela Sanz-Alcazar, Elena Britti, Fabien Delaspre, Elisa Cabiscol, Joaquim Ros, Jordi Tamarit; bioRxiv 2021.04.05.438486; doi: doi:10.1101/2021.04.05.438486 

In the present work, we have characterized a new mouse model of FA (FXNI151F) based on a pathological point mutation (I154F) present in some FA patients. These mice present very low frataxin levels in all tissues and display neurological deficits resembling those observed in FA patients. We have also observed decreased content of components from OXPHOS complexes I and II, decreased aconitase activity, and alterations in the antioxidant defenses. Remarkably, these biochemical alterations precede the appearance of neurological symptoms and present a different profile in heart and brain or cerebellum. The FXNI151F mouse is an excellent tool for analyzing the consequences of frataxin deficiency in different tissues and for testing new therapies.

Synthesis of 5‐[(1H‐indol‐3‐yl)methyl]‐1,3,4‐oxadiazole‐2(3H)‐thiones and their protective activity against oxidative stress

škauskienė, M., Kadlecová, A., Voller, J., Janovská, L., Malinauskienė, V., Žukauskaitė, A., Šačkus, A., Arch. Pharm. 2021, e2100001. doi:10.1002/ardp.202100001

A series of 5‐[(1H‐indol‐3‐yl)methyl]‐1,3,4‐oxadiazole‐2(3H)‐thiones was synthesized in this study. Methyl substitution on the indole ring and propyl, butyl, or benzyl substitution on sulfhydryl group‐possessing compounds were revealed to protect Friedreich's ataxia fibroblasts against chemically induced oxidative stress. Two of the active compounds also reproducibly increased the survival of Caenorhabditis elegans exposed to juglone‐induced oxidative stress.

Lessons for clinical trial design in Friedreich's ataxia

Masha G Savelieff Eva L Feldman The Lancet Neurology; Published:March 23, 2021DOI:https://doi.org/10.1016/S1474-4422(21)00064-8 Friedreich's ataxia is a rare autosomal-recessive disease caused by mutations in the FXN gene, which encodes frataxin, a mitochondrial protein.  It is the most common inherited ataxia, which usually manifests as gait unsteadiness in adolescence, with slowly progressive trunk and limb ataxia, and eventual loss of independent movement.  Friedreich's ataxia often involves the heart and musculoskeletal system and raises diabetes risk, making it a multisystem disorder.

Rare-disease researchers face unique obstacles: Minoryx

29-Mar-2021 By Jenni Spinner A representative of the rare-disease specialist firm outlines the unique obstacles of orphan CNS disease research, and how professionals can overcome them.

Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en EspañaEpidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study

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 Munain, G. Fernández García 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. Echevarría 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; Neurología, 2021, doi:10.1016/j.nrl.2021.01.006. 

 We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia.