Rosa, P.L.; Bertini, E.S.; Piemonte, F.; Int. J. Mol. Sci. 2020, 21, 916. doi:10.3390/ijms21030916
Frataxin depletion impairs iron–sulfur cluster biosynthesis and determines iron accumulation in the mitochondria. Mounting evidence suggests that these defects increase oxidative stress susceptibility and reactive oxygen species production in FA, where the pathologic picture is worsened by a defective regulation of the expression and signaling pathway modulation of the transcription factor NF-E2 p45-related factor 2 (NRF2), one of the fundamental mediators of the cellular antioxidant response. NRF2 protein downregulation and impairment of its nuclear translocation can compromise the adequate cellular response to the frataxin depletion-dependent redox imbalance. As NRF2 stability, expression, and activation can be modulated by diverse natural and synthetic compounds, efforts have been made in recent years to understand if regulating NRF2 signaling might ameliorate the pathologic defects in FA. Here we provide an analysis of the pharmaceutical interventions aimed at restoring the NRF2 signaling network in FA, elucidating specific biomarkers useful for monitoring therapeutic effectiveness, and developing new therapeutic tools.
Friday, January 31, 2020
Tuesday, January 28, 2020
Europe’s drug regulator wins court backing for data transparency policy
Clare Dyer, BMJ 2020;368:m302
The European Union’s highest court has decisively upheld the European Medicines Agency’s right to publish clinical trial data from drug companies’ applications to market their products in the EU.
In two keenly awaited judgments, the European Court of Justice has comprehensively rejected appeals by two companies against rulings in 2018 by the General Court of the European Union upholding the European Medicines Agency’s open data policy.12
In 2010 the agency adopted a policy of making available all documents underlying a successful drug licence application from January 2014, setting aside its previous presumption of confidentiality. But the move was resisted by pharmaceutical companies, which mounted legal challenges, arguing that their commercial confidentiality was at risk.
The European Union’s highest court has decisively upheld the European Medicines Agency’s right to publish clinical trial data from drug companies’ applications to market their products in the EU.
In two keenly awaited judgments, the European Court of Justice has comprehensively rejected appeals by two companies against rulings in 2018 by the General Court of the European Union upholding the European Medicines Agency’s open data policy.12
In 2010 the agency adopted a policy of making available all documents underlying a successful drug licence application from January 2014, setting aside its previous presumption of confidentiality. But the move was resisted by pharmaceutical companies, which mounted legal challenges, arguing that their commercial confidentiality was at risk.
Monday, January 27, 2020
Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
Jean-Michel Heard, Charlotte Vrinten, Michael Schlander, Cinzia Maria Bellettato, Corine van Lingen, Maurizio Scarpa & the MetabERN collaboration group. Orphanet J Rare Dis 15, 3 (2020) doi:10.1186/s13023-019-1280-5
It was not the scope of this study to examine the impact of treatment costs, which was debated elsewhere, but rather to bring some indications on benefits for patient populations that are relevant to the assessment of treatment value. More accurate assessment of patient’s population benefit would require measuring markers of disease natural history and patient’s quality of life in treated patient cohorts and analysis of the results by all stakeholders, including HCPs, patients and families. Such methodological approach is needed to ensuring appropriate assessment of marketed treatment value and adapted decision on reimbursement. It is also desirable that end-users and public policy makers are involved at early steps of product development, in order to estimate the potential and/or expected value of the candidate treatments that are selected for development and future marketing. This might reduce the risk of developing and marketing products that do not adequately meet patient’s needs, and might optimize priority investments for OMPs.
It was not the scope of this study to examine the impact of treatment costs, which was debated elsewhere, but rather to bring some indications on benefits for patient populations that are relevant to the assessment of treatment value. More accurate assessment of patient’s population benefit would require measuring markers of disease natural history and patient’s quality of life in treated patient cohorts and analysis of the results by all stakeholders, including HCPs, patients and families. Such methodological approach is needed to ensuring appropriate assessment of marketed treatment value and adapted decision on reimbursement. It is also desirable that end-users and public policy makers are involved at early steps of product development, in order to estimate the potential and/or expected value of the candidate treatments that are selected for development and future marketing. This might reduce the risk of developing and marketing products that do not adequately meet patient’s needs, and might optimize priority investments for OMPs.
Sunday, January 26, 2020
Correlation of Visual Quality of Life With Clinical and Visual Status in Friedreich Ataxia
Afsharian P, Nolan-Kenney R, Lynch AE, Balcer LJ, Lynch DR.; J Neuroophthalmol. 2020 Jan 17. doi: 10.1097/WNO.0000000000000878.
Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function.
Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function.
Saturday, January 25, 2020
Modeling cardiac dysfunction of Friedreich's ataxia using ventricular sheets, tissues and chambers engineered from human pluripotent stem cells
Andy O.-T. Wong, Deborah K. Lieu, Gabriel K. Wong, Bimal Gurung, Wan Wai Tse, Kevin D. Costa, Camie W. Chan, Joseph D. Nabhan, Ronald A. Li; Journal of Pharmacological and Toxicological Methods, Volume 99, 2019, 106595, doi:10.1016/j.vascn.2019.05.175.
We conclude that these humanbased FRDA models provide a biomimetic platform suitable to facilitate the studies of disease pathogenesis and pharmaceutical testing.
We conclude that these humanbased FRDA models provide a biomimetic platform suitable to facilitate the studies of disease pathogenesis and pharmaceutical testing.
Friday, January 24, 2020
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.
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.
Thursday, January 23, 2020
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.
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.
Wednesday, January 22, 2020
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.
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.
Tuesday, January 21, 2020
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.
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.
Monday, January 20, 2020
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.
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.
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