Antioxidants & Redox Signaling. doi:10.1089/ars.2011.3969.
Robin A Smith, Dunedin, New Zealand; Richard C Hartley, Glasgow, United Kingdom; MIke Murphy, MRC, Mitochondrial Biology Unit, Cambridge, United Kingdom
Monday, March 14, 2011
Saturday, March 12, 2011
Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA).
Am Heart J. 2011 Mar;161(3):639-645.e1. Epub 2011 Jan 31.
Lagedrost SJ, Sutton MS, Cohen MS, Satou GM, Kaufman BD, Perlman SL, Rummey C, Meier T, Lynch DR.
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; The Children's Hospital of Philadelphia, Philadelphia, PA.
CONCLUSIONS: The study does not provide evidence of benefit in this cohort over a 6-month treatment period.
Lagedrost SJ, Sutton MS, Cohen MS, Satou GM, Kaufman BD, Perlman SL, Rummey C, Meier T, Lynch DR.
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; The Children's Hospital of Philadelphia, Philadelphia, PA.
CONCLUSIONS: The study does not provide evidence of benefit in this cohort over a 6-month treatment period.
A Combined Nucleic Acid and Protein Analysis in Friedreich Ataxia: Implications for Diagnosis, Pathogenesis and Clinical Trial Design
PLoS ONE 6(3): e17627. doi:10.1371/journal.pone.0017627
Francesco Saccà1*, Giorgia Puorro1, Antonella Antenora1, Angela Marsili1, Alessandra Denaro1, Raffaele Piro1, Pierpaolo Sorrentino1, Chiara Pane1, Alessandra Tessa2, Vincenzo Brescia Morra1, Sergio Cocozza3, Giuseppe De Michele1, Filippo M. Santorelli2, Alessandro Filla1
1 Department of Neurological Sciences, University Federico II, Naples, Italy, 2 Molecular Medicine, IRCCS Stella Maris, Pisa, Italy, 3 Department of Cellular and Molecular Biology, University Federico II, Naples, Italy
OPEN ACCESS
Methodology/Principal Findings
We enrolled 24 patients with classic FRDA phenotype (cFA), 6 late onset FRDA (LOFA), all homozygous for GAA expansion, 5 pFA cases who harbored the GAA expansion in compound heterozygosis with FXN point mutations (namely, p.I154F, c.482+3delA, p.R165P), 33 healthy expansion carriers, and 29 healthy controls. DNA was genotyped for GAA expansion, mRNA/FXN was quantified in real-time, and frataxin protein was measured using lateral-flow immunoassay in peripheral blood mononuclear cells (PBMCs). Mean residual levels of frataxin, compared to controls, were 35.8%, 65.6%, 33%, and 68.7% in cFA, LOFA, pFA and healthy carriers, respectively. Comparison of both cFA and pFA with controls resulted in 100% sensitivity and specificity, but there was overlap between LOFA, carriers and controls. Frataxin levels correlated inversely with GAA1 and GAA2 expansions, and directly with age at onset. Messenger RNA expression was reduced to 19.4% in cFA, 50.4% in LOFA, 52.7% in pFA, 53.0% in carriers, as compared to controls (p<0.0001). mRNA levels proved to be diagnostic when comparing cFA with controls resulting in 100% sensitivity and specificity. In cFA and LOFA patients mRNA levels correlated directly with protein levels and age at onset, and inversely with GAA1 and GAA2.
FULL TEXT PDF
Francesco Saccà1*, Giorgia Puorro1, Antonella Antenora1, Angela Marsili1, Alessandra Denaro1, Raffaele Piro1, Pierpaolo Sorrentino1, Chiara Pane1, Alessandra Tessa2, Vincenzo Brescia Morra1, Sergio Cocozza3, Giuseppe De Michele1, Filippo M. Santorelli2, Alessandro Filla1
1 Department of Neurological Sciences, University Federico II, Naples, Italy, 2 Molecular Medicine, IRCCS Stella Maris, Pisa, Italy, 3 Department of Cellular and Molecular Biology, University Federico II, Naples, Italy
OPEN ACCESS
Methodology/Principal Findings
We enrolled 24 patients with classic FRDA phenotype (cFA), 6 late onset FRDA (LOFA), all homozygous for GAA expansion, 5 pFA cases who harbored the GAA expansion in compound heterozygosis with FXN point mutations (namely, p.I154F, c.482+3delA, p.R165P), 33 healthy expansion carriers, and 29 healthy controls. DNA was genotyped for GAA expansion, mRNA/FXN was quantified in real-time, and frataxin protein was measured using lateral-flow immunoassay in peripheral blood mononuclear cells (PBMCs). Mean residual levels of frataxin, compared to controls, were 35.8%, 65.6%, 33%, and 68.7% in cFA, LOFA, pFA and healthy carriers, respectively. Comparison of both cFA and pFA with controls resulted in 100% sensitivity and specificity, but there was overlap between LOFA, carriers and controls. Frataxin levels correlated inversely with GAA1 and GAA2 expansions, and directly with age at onset. Messenger RNA expression was reduced to 19.4% in cFA, 50.4% in LOFA, 52.7% in pFA, 53.0% in carriers, as compared to controls (p<0.0001). mRNA levels proved to be diagnostic when comparing cFA with controls resulting in 100% sensitivity and specificity. In cFA and LOFA patients mRNA levels correlated directly with protein levels and age at onset, and inversely with GAA1 and GAA2.
FULL TEXT PDF
Friday, March 11, 2011
Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model
Neurobiology of Disease, doi:10.1016/j.nbd.2011.02.016
Chiranjeevi Sandi a, Ricardo Mouro Pinto a, 1, Sahar Al-Mahdawi a, Vahid Ezzatizadeh a, Glenn Barnes b, Steve Jones b, James R. Rusche b, Joel M. Gottesfeld c and Mark A. Pook a
a Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UB8 3PH, UK
b Repligen Corporation, Waltham, MA, USA
c Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA
Available online 10 March 2011.
keywords: Friedreich ataxia (FRDA), Histone deacetylase (HDAC) inhibitors, pimelic o-aminobenzamide compounds 106, 109 and 136, FXN gene silencing, short-term studies, long-term therapeutic effects, FRDA mouse model.
Chiranjeevi Sandi a, Ricardo Mouro Pinto a, 1, Sahar Al-Mahdawi a, Vahid Ezzatizadeh a, Glenn Barnes b, Steve Jones b, James R. Rusche b, Joel M. Gottesfeld c and Mark A. Pook a
a Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UB8 3PH, UK
b Repligen Corporation, Waltham, MA, USA
c Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA
Available online 10 March 2011.
keywords: Friedreich ataxia (FRDA), Histone deacetylase (HDAC) inhibitors, pimelic o-aminobenzamide compounds 106, 109 and 136, FXN gene silencing, short-term studies, long-term therapeutic effects, FRDA mouse model.
Thursday, March 10, 2011
Clinical proof of concept patient trials for OX1 in Friedreich's Ataxia
Intellect Neurosciences, Inc. is a Manhattan-based biopharmaceutical company
The Company's most advanced internally developed product is OX1 which has been tested in Phase 1 clinical trials. The Company plans to conduct clinical proof of concept patient trials for OX1 in Alzheimer's disease and Friedreich's Ataxia,
Wednesday, March 9, 2011
New Robot To Help People To Walk Again
Medical News Today, Article Date: 09 Mar 2011
"Over the four-year period, the project will produce two demonstrators, among them a novel mobile robot-assisted gait rehabilitation system which will be a self-aware system capable of learning to enable it to optimally match the requirements of the user at different stages of rehabilitation."
"Over the four-year period, the project will produce two demonstrators, among them a novel mobile robot-assisted gait rehabilitation system which will be a self-aware system capable of learning to enable it to optimally match the requirements of the user at different stages of rehabilitation."
Monday, March 7, 2011
Regulation of chromatin by histone modifications
Cell Research (2011) 21:381–395. doi:10.1038/cr.2011.22;
Andrew J Bannister1 and Tony Kouzarides1
1The Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK
Keywords:
histone; modifications; chromatin
Full text pdf
Andrew J Bannister1 and Tony Kouzarides1
1The Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK
Keywords:
histone; modifications; chromatin
Full text pdf
Saturday, March 5, 2011
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
Nature Biotechnology, Year published:(2011), doi:10.1038/nbt.1759
1. Cellzome AG, Heidelberg, Germany.
Marcus Bantscheff, Carsten Hopf, Mikhail M Savitski, Antje Dittmann, Paola Grandi, Anne-Marie Michon, Judith Schlegl, Yann Abraham, Isabelle Becher, Giovanna Bergamini, Markus Boesche, Manja Delling, Birgit Dümpelfeld, Dirk Eberhard, Carola Huthmacher, Toby Mathieson, Daniel Poeckel, Katja Strunk, Gavain Sweetman, Ulrich Kruse, Gitte Neubauer & Gerard Drewes
2. Cellzome Ltd., Chesterford Research Park, Cambridge, United Kingdom.
Valérie Reader & Nigel G Ramsden
1. Cellzome AG, Heidelberg, Germany.
Marcus Bantscheff, Carsten Hopf, Mikhail M Savitski, Antje Dittmann, Paola Grandi, Anne-Marie Michon, Judith Schlegl, Yann Abraham, Isabelle Becher, Giovanna Bergamini, Markus Boesche, Manja Delling, Birgit Dümpelfeld, Dirk Eberhard, Carola Huthmacher, Toby Mathieson, Daniel Poeckel, Katja Strunk, Gavain Sweetman, Ulrich Kruse, Gitte Neubauer & Gerard Drewes
2. Cellzome Ltd., Chesterford Research Park, Cambridge, United Kingdom.
Valérie Reader & Nigel G Ramsden
Friday, March 4, 2011
Frataxin participates to the hypoxia-induced response in tumors
Cell Death and Disease (2011) 2, e123; doi:10.1038/cddis.2011.5
Guccini I, Serio D, Condò I, Rufini A, Tomassini B, Mangiola A, Maira G, Anile C, Fina D, Pallone F, Mongiardi MP, Levi A, Ventura N, Testi R, Malisan F
Keywords: frataxin, Friedreich's ataxia, oxidative stress, apoptosis, tumor suppressor, stress resistance, tumor cells, response to hypoxic stress, hypoxia-inducible factors (HIF), tumor-suppressor p53.
"frataxin is in fact increased in human tumors in vivo"
"Frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression"
Guccini I, Serio D, Condò I, Rufini A, Tomassini B, Mangiola A, Maira G, Anile C, Fina D, Pallone F, Mongiardi MP, Levi A, Ventura N, Testi R, Malisan F
Keywords: frataxin, Friedreich's ataxia, oxidative stress, apoptosis, tumor suppressor, stress resistance, tumor cells, response to hypoxic stress, hypoxia-inducible factors (HIF), tumor-suppressor p53.
"frataxin is in fact increased in human tumors in vivo"
"Frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression"
Wednesday, March 2, 2011
Cardiomyopathy of Friedreich's Ataxia: Use of Mouse Models to Understand Human Disease and Guide Therapeutic Development.
Pediatr Cardiol. 2011 Mar 1. [Epub ahead of print]
Payne RM, Pride PM, Babbey CM.
Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut, R4302, Indianapolis, IN, 46202, USA
Keywords: Friedreich's ataxia, heart, brain, severe cardiomyopathy, heart failure, frataxin, Animal models, to develop new therapeutic strategies.
Payne RM, Pride PM, Babbey CM.
Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut, R4302, Indianapolis, IN, 46202, USA
Keywords: Friedreich's ataxia, heart, brain, severe cardiomyopathy, heart failure, frataxin, Animal models, to develop new therapeutic strategies.
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