Frataxin deficiency induces lipid accumulation and affects thermogenesis in brown adipose tissue

Riccardo Turchi, Flavia Tortolici, Giulio Guidobaldi, Federico Iacovelli, Mattia Falconi, Stefano Rufini, Raffaella Faraonio, Viviana Casagrande, Massimo Federici, Lorenzo De Angelis, Simone Carotti, Maria Francesconi, Maria Zingariello, Sergio Morini, Roberta Bernardini, Maurizio Mattei, Piergiorgio La Rosa, Fiorella Piemonte, Daniele Lettieri-Barbato & Katia Aquilano; Death Dis 11, 51 (2020). doi:10.1038/s41419-020-2253-2

FXN deficiency in mice leads to clinical-pathological features parallel to those observed in diabetic patients. Among the metabolic parameters we have evidenced that the lipolytic and thermogenic activities of BAT are reduced, thus providing the possibilities of targeting BAT that might result in therapeutic benefits in FRDA.

Frataxin Structure and Function

Ignacio Hugo Castro, María Florencia Pignataro, Karl Ellioth Sewell, Lucía Daniela Espeche, María Georgina Herrera, Martín Ezequiel Noguera, Liliana Dain, Alejandro Daniel Nadra, Martín Aran, Clara Smal, Mariana Gallo, Javier Santos(2019). Frataxin Structure and Function. In: Harris J., Marles-Wright J. (eds) Macromolecular Protein Complexes II: Structure and Function. Subcellular Biochemistry, vol 93. Springer, Cham. DOI:10.1007/978-3-030-28151-9_13

By combining multiple experimental tools including high resolution techniques like NMR and X-ray, but also SAXS, crosslinking and mass-spectrometry, it was possible to build a reliable model of the structure of the desulfurase supercomplex NFS1/ACP-ISD11/ISCU/frataxin. In this chapter, we explore these issues showing how the scientific view concerning frataxin structure-function relationships has evolved over the last years.

Expresión de IRS2 en ratones afectados con ataxia de Friedreich

Gil Carceller, B. (2019). Grau en Biotecnologia, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural.

CONCLUSIONES
1. Se ha realizado un estudio de perfil de expresión génica en tejidos aislados (cerebro, cerebelo, músculo, hígado y páncreas) de ratones wt versus ratones YG8R (ataxia de Friedreich) con el
objetivo de establecer una posible relación de la FRDA con la diabetes tipo 2.
2. Se ha establecido un gen constitutivo o Housekeeping, Hprt, que permite el análisis de la expresión génica en todos los tejidos en este estudio.
3. Se han observado diferencias significativas en cerebro (aumento de expresión de Irs1, Irs2, InsR e Igf1), cerebelo (disminución de expresión de Irs1, Irs2 e InsR) y músculo (disminución de
expresión de Irs1 y aumento de expresión de Irs2).
4. Se ha analizado Ucp2 por su implicación en la función mitocondrial y posible relación con la diabetes y la FRDA.
5. Existen evidencias que indican una posible relación de FRDA con la diabetes tipo 2 a nivel de expresión génica.

Can this San Diego startup mimic exercise and fasting with a pill? Epirium raises $85M to find out

San Diego Union Tribune, BRITTANY MEILING, JAN. 13, 2020

A biotech startup in La Jolla has raised $85 million from notable science investors to investigate its idea for treating age-related diseases: a pill that mimics the effects of exercise and fasting.
The company, called Epirium Bio, says its scientists have discovered a new human hormone, which, when influenced, can trigger the production of more mitochondria. The depletion of the body’s mitochondria — a.k.a. “engines” of cells — is at the core of many age-related human illnesses.
To start, Epirium will be tackling rare muscle disorders, such as Duchenne muscular dystrophy, Becker muscular dystrophy and Friedreich’s ataxia.

Education and information needs for physicians about rare diseases in Spain

Enrique Ramalle-Gómara, Elena Domínguez-Garrido, María Gómez-Eguílaz, María Eugenia Marzo-Sola, José Luis Ramón-Trapero & Josefa Gil-de-Gómez; J Rare Dis 15, 18 (2020) doi:10.1186/s13023-019-1285-0

In conclusion, the study supports other investigations that have shown that clinicians lack easy access to educational opportunities and information resources regarding rare diseases. It is imperative that the public health system includes ongoing training on rare diseases in programs to improve the training of physicians in both primary care and specialized care.

Very-late-onset Friedreich’s ataxia: diagnosis in a kindred with late-onset cerebellar ataxia

Conor Fearon, Roisin Lonergan, Damien Ferguson, Susan Byrne, David Bradley, Yvonne Langan, Janice Redmond; Neurology 2020;20:55-58. doi:10.1136/practneurol-2019-002368

We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich’s ataxia and discuss the pitfalls and risk of misdiagnosis.

Frataxin deficiency in Friedreich’s ataxia is associated with reduced levels of HAX-1, a regulator of cardiomyocyte death and survival

Francesca Tiano, Francesca Amati, Fabio Cherubini, Elena Morini, Chiara Vancheri, Sara Maletta, Silvia Fortuni, Dario Serio, Andrea Quatrana, Riccardo Luffarelli, Monica Benini, Giulia Alfedi, Luca Panarello, Alessandra Rufini, Nicola Toschi, Marina Frontali, Silvia Romano, Christian Marcotulli, Carlo Casali, Silvia Gioiosa, Caterina Mariotti, Alessia Mongelli, Mario Fichera, Ivano Condò, Giuseppe Novelli, Roberto Testi, Florence Malisan; Human Molecular Genetics, , ddz306, doi:10.1093/hmg/ddz306

Our results suggest that HAX-1 could be considered as a potential biomarker of cardiac disease in FRDA and the evaluation of its expression might provide insights into its pathogenesis as well as improving risk stratification strategies.

PTC Therapeutics (PTCT) Presents At 38th Annual J.P. Morgan Healthcare Conference - Slideshow

seekingalpha. Jan. 16, 2020

Slide deck was published by PTC Therapeutics, Inc. in conjunction with this event.

Novartis' David Lennon on next steps for AveXis, selling Zolgensma's price to the public

BioPharma Dive (WEB 01/16/2020)

SAN FRANCISCO — Novartis sparked a new round of drug pricing criticism last May when the Swiss pharma revealed its new gene therapy Zolgensma would cost $2.1 million per patient.

Pipeline products to prioritize: "Those programs existed as part of the acquisition of AveXis. Since then, we started partnering with [the Novartis Institutes of Biomedical Research] to apply this platform to different diseases. The first one we announced is a project for Friedreich's ataxia, a muscle-wasting disease."

Safety and Efficacy of Interferon γ in Friedreich's Ataxia

Marinela Vavla MD PhD Maria Grazia D'Angelo MD PhD Filippo Arrigoni MD Nicola Toschi PhD Denis Peruzzo PhD Sandra Gandossini MD Annamaria Russo MD Eleonora Diella Stefania Tirelli PhD Roberto Salati MD Paolo Scarpazza MD Riccardo Luffarelli PhD Silvia Fortuni PhD Alessandra Rufini PhD Ivano Condò PhD Roberto Testi MD Andrea Martinuzzi MD PhD; Mov Disord. 2020 doi:10.1002/mds.27979

A relevant indication that emerges from the study, the previously studies, and from the numerous FRDA patients using IFNγ off label is the possible presence of nonresponders. A randomized withdrawal design is therefore best suited to increase the power of future clinical trials to definitively assess the efficacy of IFNγ treatment in FRDA