Por GENÉTICA MÉDICA · 11 de octubre de 2015
¿Estamos más cerca de un tratamiento efectivo?
Si pensamos que cuando se identificó el gen no se tenía ninguna idea de cuál podría ser su función y que ahora ya se está evaluando el efecto terapéutico de un número importante de moléculas, mi respuesta es que sí. Pero también es cierto, que a pesar de los años de investigación todavía no se ha conseguido un tratamiento que sea realmente eficaz. No es nada fácil el tratamiento de las enfermedades genéticas, pero está claro que hoy conocemos qué les ocurre a las células sin frataxina y por lo tanto, se está en disposición de poder desarrollar estrategias que sean realmente útiles para el tratamiento de esta enfermedad. Leer mas....
Monday, October 12, 2015
A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency
Alexandra Seguin, Véronique Monnier, Amandine Palandri, Frédéric Bihel, Michael Rera, Martine Schmitt, Jean-Michel Camadro, Hervé Tricoire, and Emmanuel Lesuisse; Oxidative Medicine and Cellular Longevity, Volume 2015 (2015), Article ID 565140, 10 pages DOI: 10.1155/2015/565140
The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy.
The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy.
Saturday, October 10, 2015
Acoustic Analyses of Prolonged Vowels in Young Adults With Friedreich Ataxia
Cecyle Carson, Jack Ryalls, Kaylea Hardin-Hollingsworth, Marie-Therese Le Normand, Bari Ruddy, Journal of Voice, Available online 9 October 2015, ISSN 0892-1997, doi:10.1016/j.jvoice.2015.05.008.
The purpose of this study was to determine which cepstral- and spectral-based measures extracted from prolonged vowels using Analysis of Dysphonia in Speech and Voice (ADSV) program discriminate between those who have FA and normal voice (NV) peers.
The purpose of this study was to determine which cepstral- and spectral-based measures extracted from prolonged vowels using Analysis of Dysphonia in Speech and Voice (ADSV) program discriminate between those who have FA and normal voice (NV) peers.
Tuesday, October 6, 2015
Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment
Marek Napiontek , Krzysztof Pietrzak; European Journal of Orthopaedic Surgery & Traumatology February 2015, Volume 25, Issue 2, pp 391-397 DOI 10.1007/s00590-014-1498-9
The purpose of the paper was to present the results of surgical treatment of foot deformities in peripheral neuropathies using bone procedures: both joint preserving and with joint arthrodesis. The study included patients presented Charcot–Marie–Tooth disease, Friedreich’s ataxia and peripheral motor and sensory neuropathies of undetermined nature. The results show that none of the surgical techniques used for correction of foot deformities in motor-sensory polyneuropathies seems to be preferable.
The purpose of the paper was to present the results of surgical treatment of foot deformities in peripheral neuropathies using bone procedures: both joint preserving and with joint arthrodesis. The study included patients presented Charcot–Marie–Tooth disease, Friedreich’s ataxia and peripheral motor and sensory neuropathies of undetermined nature. The results show that none of the surgical techniques used for correction of foot deformities in motor-sensory polyneuropathies seems to be preferable.
Monday, October 5, 2015
Pathology of Intercalated Discs in Friedreich Cardiomyopathy
R. Liane Ramirez, MS; Alyssa B. Becker, BA; Joseph E. Mazurkiewicz, PhD; Paul J. Feustel, PhD; Benjamin B. Gelman, MD, PhD; Arnulf H. Koeppen, MD, J Am Coll Cardiol. 2015;66(15):1739-1740. doi:10.1016/j.jacc.2015.06.1355
The underlying mutation in FA causes frataxin deficiency, which may adversely affect ICDs and GJs before the onset of heart disease and perhaps prenatally.
The underlying mutation in FA causes frataxin deficiency, which may adversely affect ICDs and GJs before the onset of heart disease and perhaps prenatally.
Friday, October 2, 2015
Cold Denaturation Unveiled: the Molecular Mechanism of Asymmetric Unfolding of Yeast Frataxin
Domenico Sanfelice, Edoardo Morandi, Annalisa Pastore, Neri Niccolai andPiero Andrea Temussi; ChemPhysChem 1439-7641 (2015), DOI 10.1002/cphc.201500765
Monday, September 28, 2015
A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia
Francoise Pousset, MD; Lise Legrand, MD; Marie-Lorraine Monin, MD; Claire Ewenczyk, MD; Perrine Charles, MD, PhD; Michel Komajda, MD; Alexis Brice, MD; Massimo Pandolfo, MD; Richard Isnard, MD, PhD; Sophie Tezenas du Montcel, MD, PhD; Alexandra Durr, MD, PhD. JAMA Neurol. Published online September 28, 2015. doi:10.1001/jamaneurol.2015.1855
Survival in FRDA is determined by cardiac complications, which are dependent on the mutation. The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time. Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.
Survival in FRDA is determined by cardiac complications, which are dependent on the mutation. The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time. Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.
Monitoring Cardiac Function During Idebenone Therapy in Friedreich's Ataxia
Di Salvo Giovanni, Pergola Valeria, Fadel Bahaa and Al Fayyadh Majid, Current Pharmaceutical Design 21-4, Page: [479 - 483] DOI: 10.2174/138161282104141204142917
This drug has the potential to preserve and even improve mitochondrial function.Studies on Idebenone treatment showed rather conflicting results on FA cardiomyopathy. The present article reviews the clinical features of FA cardiomyopathy, imaging techniques used to diagnose, follow and monitor therapy which aimed to revert FA cardiomyopathy.
This drug has the potential to preserve and even improve mitochondrial function.Studies on Idebenone treatment showed rather conflicting results on FA cardiomyopathy. The present article reviews the clinical features of FA cardiomyopathy, imaging techniques used to diagnose, follow and monitor therapy which aimed to revert FA cardiomyopathy.
Saturday, September 26, 2015
Expanded GAA repeats impede transcription elongation through the FXN gene and induce transcriptional silencing that is restricted to the FXN locus
Yanjie Li, Yue Lu, Urszula Polak, Kevin Lin, Jianjun Shen, Jennifer Farmer, Lauren Seyer, Angela D. Bhalla, Natalia Rozwadowska, David R. Lynch, Jill Sergesketter Butler and Marek Napierala; Hum. Mol. Genet. (2015) doi: 10.1093/hmg/ddv397, First published online: September 23, 2015
The GAA-induced silencing effect does not influence expression of neighboring genes upstream or downstream of FXN. The results indicate that approaches aimed to reactivate frataxin expression should simultaneously address deficits in transcription initiation and elongation at the FXN locus.
The GAA-induced silencing effect does not influence expression of neighboring genes upstream or downstream of FXN. The results indicate that approaches aimed to reactivate frataxin expression should simultaneously address deficits in transcription initiation and elongation at the FXN locus.
Thursday, September 24, 2015
FXN Promoter Silencing in the Humanized Mouse Model of Friedreich Ataxia
Chutake YK, Costello WN, Lam CC, Parikh AC, Hughes TT, Michalopulos MG, Mark A. Pook, Sanjay I. Bidichandani. (2015) FXN Promoter Silencing in the Humanized Mouse Model of Friedreich Ataxia. PLoS ONE 10(9): e0138437. doi:10.1371/journal.pone.0138437
OPEN ACCESS
Our results indicate that FXN transcriptional deficiency in the YG8sR humanized mouse model of FRDA is caused by deficient transcriptional initiation as a result of promoter silencing. While this mechanism has previously been noted in patient-derived lymphoblastoid cell lines, our present data provide supportive evidence for the existence of this mechanism of transcriptional deficiency in fibroblasts and in multiple tissues. Our data also suggest that the mechanism underlying FXN transcriptional deficiency in FRDA is unlikely to be tissue-specific.
Our data indicate that the YG8sR humanized mouse is a reasonable model for investigating the molecular mechanism(s) underlying repeat-mediated promoter silencing in FRDA. The YG8sR mouse model would also be useful for testing drugs that are designed to reverse the transcriptional initiation defect caused by promoter silencing in FRDA, such as the 2-aminobenzamide derived histone deacetylase inhibitors.
OPEN ACCESS
Our results indicate that FXN transcriptional deficiency in the YG8sR humanized mouse model of FRDA is caused by deficient transcriptional initiation as a result of promoter silencing. While this mechanism has previously been noted in patient-derived lymphoblastoid cell lines, our present data provide supportive evidence for the existence of this mechanism of transcriptional deficiency in fibroblasts and in multiple tissues. Our data also suggest that the mechanism underlying FXN transcriptional deficiency in FRDA is unlikely to be tissue-specific.
Our data indicate that the YG8sR humanized mouse is a reasonable model for investigating the molecular mechanism(s) underlying repeat-mediated promoter silencing in FRDA. The YG8sR mouse model would also be useful for testing drugs that are designed to reverse the transcriptional initiation defect caused by promoter silencing in FRDA, such as the 2-aminobenzamide derived histone deacetylase inhibitors.
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