Genetic Variations Creating MicroRNA Target Sites in the FXN 3′-UTR Affect Frataxin Expression in Friedreich Ataxia.

Genetic Variations Creating MicroRNA Target Sites in the FXN 3′-UTR Affect Frataxin Expression in Friedreich Ataxia. Simonetta Bandiera ,François Cartault, Anne-Sophie Jannot, Elie Hatem, Muriel Girard, Laila Rifai, Clemence Loiseau, Arnold Munnich, Stanislas Lyonnet, Alexandra Henrion-Caude. (2013)PLoS ONE 8(1): e54791. doi:10.1371/journal.pone.0054791

We found that this FRDA 3′-UTR conferred a 1.2-fold decrease in the expression of a reporter gene versus the alternative haplotype configuration. We established that differential targeting by miRNA could account for this functional variability. We specifically demonstrated the involvement of miR-124 (i.e hsa-mir-124-3p) in the down-regulation of FRDA-3′-UTR. Our results suggest for the first time that post-transcriptional regulation of frataxin occurs through the 3′-UTR and involves miRNA targeting. We propose that the involvement of miRNAs in a FRDA-specific regulation of frataxin may provide a rationale to increase residual levels of frataxin through miRNA-inhibitory molecules.

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Friedreich Ataxia Global Clinical Trials Review, H1, 2013

Friedreich Ataxia Global Clinical Trials Review, H1, 2013.

This report provides elemental information and data relating to the clinical trials on Friedreich Ataxia. It includes an overview of the trial numbers and their recruitment status as per the site of trial conduction across the globe.

The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

The role of aberrant mitochondrial bioenergetics in diabetic neuropathy. Chowdhury SK, Smith DR, Fernyhough P; Neurobiology of Disease [2013, 51:56-65]

The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich ataxia, Charcot-Marie-Tooth disease type 2 .....

Rating disease progression of Friedreich’s ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database

Rating disease progression of Friedreich’s ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database . Günther Metz, Nicholas Coppard, Jonathon M. Cooper, Martin B. Delatycki, Alexandra Dürr, Nicholas A. Di Prospero, Paola Giunti, David R. Lynch8, J. B. Schulz, Christian Rummey and Thomas Meier. Brain (2013) 136 (1): 259-268. doi: 10.1093/brain/aws309

Keywords: cross-sectional study, disease progression in Friedreich’s ataxia, International Cooperative Ataxia Rating Scale, function of disease duration, age of onset, GAA repeat lengths.

Subvention importante

Subvention importante . CAFA, Canadian Association for Familial Ataxias - Claude St-Jean Foundation.

Professor Jacques P. Tremblay and his team at the CHUL laboratory in Quebec has just received a grant of $ 160,000 from the Canadian Institutes of Health Research (CIHR) for the project of inducing the production of frataxin with TALE-VP64 targeting the promoter of this protein. This will help to intensify research on Friedreich's ataxia.

Magnetic Resonance Imaging and Spectroscopy of the Central Nervous System in Friedreich's Ataxia

Magnetic Resonance Imaging and Spectroscopy of the Central Nervous System in Friedreich's Ataxia.

University of Minnesota - Clinical and Translational Science Institute

ClinicalTrials.gov Identifier: NCT01776164
First received: January 14, 2013
Last updated: January 22, 2013
Last verified: January 2013



.../... the investigators aim at utilizing the capabilities of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS). Using techniques called Diffusion Imaging, resting-state functional MRI, and Proton Spectroscopy (1H MRS), the investigators propose to determine the differences in the connectivity and neurochemistry of the spinal cord and the brain .../...

Glial Cells Assist in the Repair of Injured Nerves

Glial Cells Assist in the Repair of Injured Nerves. Max-Planck-Gesellschaft. ScienceDaily, 28 Jan. 2013. Web. 29 Jan. 2013.

Jan. 28, 2013 — Unlike the brain and spinal cord, the peripheral nervous system has an astonishing capacity for regeneration following injury. Researchers at the Max Planck Institute of Experimental Medicine in Göttingen have discovered that, following nerve damage, peripheral glial cells produce the growth factor neuregulin1, which makes an important contribution to the regeneration of damaged nerves.

Original source (Journal reference): A role for Schwann cell-derived neuregulin-1 in remyelination. Stassart RM, Fledrich R, Velanac V, Brinkmann BG, Schwab MH, Meijer D, Sereda MW, Nave KA. Nature Neuroscience, 2012; 16 (1): 48 DOI: 10.1038/nn.3281

Eye movements in patients with neurodegenerative disorders

Eye movements in patients with neurodegenerative disorders. Review, Tim J. Anderson & Michael R. MacAskill, Nature Reviews Neurology, advance online publication, Published online 22 January 2013 | doi:10.1038/nrneurol.2012.273

Keywords: neural pathways, brain regions, eye movements, cerebrum, brainstem, cerebellum, neurodegeneration, neurodegenerative disorders, disease severity, objective evaluation, saccade performance.

Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich’s ataxia YG8R mouse model

Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich’s ataxia YG8R mouse model . Dr. Yuxi Shan, Dr. Robert A Schoenfeld, Genki Hayashi, Dr. Eleonora Napoli, Dr. Tasuku Akiyama, Dr. Mirela Iodi-Carstens, Dr. Earl E. Carstens, Dr. Mark A. Pook, and Dr. Gino Cortopassi. Antioxidants & Redox Signaling. -Not available-, ahead of print. doi:10.1089/ars.2012.4537.

"Frataxin expression was significantly correlated with Nrf2 expression"

Keywords: Oxidative stress, Dorsal Root Ganglion (DRG) neurons, transcripts encoding antioxidants, peroxiredoxins, glutaredoxins, glutathione-S-transferase, antioxidant transcription factor Nrf2, frataxin, thioredoxin reductase.

Mitochondria in cardiac hypertrophy and heart failure

Mitochondria in cardiac hypertrophy and heart failure. Mariana G. Rosca, Bernard Tandler, Charles L. Hoppel. Journal of Molecular and Cellular Cardiology, Volume 55, February 2013, Pages 31-41.

Keywords: Heart failure, Cardiac hypertrophy, Mitochondria, Oxidative phosphorylation

Transition metals and mitochondrial metabolism in the heart

Transition metals and mitochondrial metabolism in the heart. Amy K. Rines, Hossein Ardehali, Journal of Molecular and Cellular Cardiology, Volume 55, February 2013, Pages 50-57. http://dx.doi.org/10.1016/j.yjmcc.2012.05.014

Highlights: "FRDA and doxorubicin toxicities are highlighted as disorders of iron deregulation.", "the heart is one of the most mitochondrially-rich tissues in the body"

The molecular basis of iron-induced oligomerization of frataxin and the role of the ferroxidation reaction in oligomerization

The molecular basis of iron-induced oligomerization of frataxin and the role of the ferroxidation reaction in oligomerization . Christopher A. G. Soderberg, Sreekanth Rajan, Aleksander V. Shkumatov, Oleksandr Gakh, Susanne Schaefer, Eva-Christina Ahlgren, Dmitri I. Svergun, Grazia Isaya and Salam Al-Karadaghi. J. Biol. Chem. jbc.M112.442285. First Published on January 23, 2013, doi:10.1074/jbc.M112.442285

Keywords: Iron-induced oligomerization, frataxin, catalyzed ferroxidation, iron availability, iron delivery.

The role of mitochondrial OXPHOS dysfunction in the development of neurologic diseases

The role of mitochondrial OXPHOS dysfunction in the development of neurologic diseases.M.E. Breuer, W.J. Koopman, S. Koene, M. Nooteboom, R.J. Rodenburg, P.H. Willems, J.A.M. Smeitink. Neurobiology of Disease, Volume 51, March 2013, Pages 27-34.

Keywords: Mitochondrial dysfunction, Neurodegenerative diseases, Bioenergetics, Cellular metabolism

Friedreich Ataxia: Neuropathology Revised.

Friedreich Ataxia: Neuropathology Revised.. Koeppen, Arnulf H. MD.; Mazurkiewicz, Jose. Journal of Neuropathology & Experimental Neurology, 72:2 2013 Feb pg 78-90.

Keywords: Friedreich ataxia, Low frataxin levels, iron-sulfur clusters, aconitase, dorsal root ganglia, dorsal columns, transsynaptic atrophy, Clarke column, dorsal spinocerebellar fibers, gracile and cuneate nuclei, sensory nerves, dentate nucleus.

Neuromuscular scoliosis

Neuromuscular scoliosis. R. Vialle, C. Thévenin-Lemoine, P. Mary; Orthopaedics & Traumatology: Surgery & Research, Available online 18 January 2013. DOI: http://dx.doi.org/10.1016/j.otsr.2012.11.002,


Highlight: "Surgical treatment of neuromuscular scoliosis differs from idiopathic scoliosis".
"Non-surgical measures rarely fully control progressive scoliosis".

Keywords: Neuromuscular scoliosis, surgical treatment, idiopathic scoliosis, complications rate, Non-surgical measures, muscular hypotonia.

The Cerebellum Looks Normal in Friedreich Ataxia.

The Cerebellum Looks Normal in Friedreich Ataxia. Mascalchi M.; AJNR Am J Neuroradiol originally published online on January 17, 2013, 10.3174/ajnr.A3480.

No abstract

Friedreich Ataxia: Dysarthria Profile and Clinical Data.

Friedreich Ataxia: Dysarthria Profile and Clinical Data. Brendel B, Ackermann H, Berg D, Lindig T, Schölderle T, Schöls L, Synofzik M, Ziegler W., Cerebellum. 2013 Jan 13. DOI http://dx.doi.org/10.1007/s12311-012-0440-0

Keywords: Friedreich ataxia (FRDA), dysarthria severity, profile of speech motor deficits, disease duration.

NAF Funded Research for FA in 2013

NAF Funded Research for FA in 2013.

Research Grants:

Generation of peripheral sensory neurons from Friedreich’s ataxia human iPS cell lines, Chintawar, Satyan, Ph.D. Université Libre de Bruxelles - Erasme Hospital, Belgium.

YOUNG INVESTIGATOR AWARDS:

Development of new mouse models of Friedreich’s Ataxia Baines, Christopher P., Ph.D., University of Missouri-Columbia, Kansas, MO

Seminar at SWOSU: “The Role of Frataxin in the Neurodegenerative Disease Friedreich’s Ataxia”

Seminar at SWOSU: “The Role of Frataxin in the Neurodegenerative Disease Friedreich’s Ataxia”.
January 10, 2013, Dr. Laura Busenlehner, assistant professor in the Department of Chemistry at the University of Alabama, will give a seminar at Southwestern Oklahoma State University on Thursday, January 17, on the Weatherford campus.

Busenlehner’s seminar is titled “The Role of Frataxin in the Neurodegenerative Disease Friedreich’s Ataxia”. Her seminar will focus on the inorganic chemistry, biochemistry and biophysical characterization of the Frataxin protein.

STATegics, Inc. Announces a New Grant from Friedreich’s Ataxia Research Alliance

STATegics, Inc. Announces a New Grant from Friedreich’s Ataxia Research Alliance. PRLog (Press Release) - Jan. 8, 2013 - Menlo Park, California.

STATegics, Inc. awarded a new grant from the Friedreich’s Ataxia Research Alliance (FARA) to advance erythropoietin receptor agonist compounds for the treatment of Friedreich’s ataxia (FRDA).

Edison Pharmaceuticals Announces Initiation of EPI-743 Phase 2B Friedreich's Ataxia Clinical Trial

Edison Pharmaceuticals Announces Initiation of EPI-743 Phase 2B Friedreich's Ataxia Clinical Trial. PR Newswire, Press release Jan. 7, 2013, 12:01 a.m. EST

MOUNTAIN VIEW, Calif., Jan. 7, 2013 /PRNewswire via COMTEX/ -- Edison Pharmaceuticals today announced the initiation of a phase 2B study entitled, "Safety and Efficacy Study of EPI-743 on Visual Function in Patients with Friedreich's Ataxia." The trial is a placebo-controlled study lasting six months, followed by an extension phase in which all subjects will receive EPI-743.

More information on study specifics is available on ClinicalTrials.gov.

Somatosensory Temporal Discrimination Threshold Is Increased in Patients with Cerebellar Atrophy

Somatosensory Temporal Discrimination Threshold Is Increased in Patients with Cerebellar Atrophy. Fiore Manganelli, Raffaele Dubbioso, Chiara Pisciotta,
Antonella Antenora, Maria Nolano, Giuseppe De Michele, Alessandro Filla, Alfredo Berardelli, Lucio Santoro. The Cerebellum, January 2013. DOI 10.1007/s12311-012-0435-x

Keywords: millisecond range, cerebellar function, somatosensory temporal discrimination threshold testing.

NeuroDNet - an open source platform for constructing and analyzing neurodegenerative disease networks

NeuroDNet - an open source platform for constructing and analyzing neurodegenerative disease networks. Suhas V Vasaikar, Aditya K Padhi, Bhyravabhotla Jayaram and James Gomes. BMC Neuroscience 2013, 14:3 doi:10.1186/1471-2202-14-3, Published: 3 January 2013

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It is in this light that we have created a database, NeuroDNet, that includes information about twelve neurodegenerative diseases - adrenomyeloneuropathy, Alzheimer disease, amyotrophic lateral sclerosis, ataxia-telangiectasia, dentatorubral-pallidoluysian atrophy, Friedreich ataxia, frontotemporal dementia, Huntington disease, Lewy body dementia, Parkinson disease, prion disease, progressive supranuclear palsy. It accounts for the interactions and regulation between signaling molecules, genes and proteins. This database is also the first of its kind, which enables the construction and analysis of NDDs through PPI, regulatory and Boolean networks. We also present the results of three case studies, which demonstrate the power of the analytical tools featured in NeuroDNet.

In Epigenomics, Location Is Everything: Researchers Exploit Gene Position to Test 'Histone Code'

In Epigenomics, Location Is Everything: Researchers Exploit Gene Position to Test 'Histone Code'. Menzies Chen, Katherine Licon, Rei Otsuka, Lorraine Pillussend, Trey Idekersend. Cell Reports, 03 January 2013

Also: Science News, Jan. 3, 2013,
Jan. 3, 2013 — In a novel use of gene knockout technology, researchers at the University of California, San Diego School of Medicine tested the same gene inserted into 90 different locations in a yeast chromosome -- and discovered that while the inserted gene never altered its surrounding chromatin landscape, differences in that immediate landscape measurably affected gene activity.