HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells

Nature Neuroscience 14, 429–436, (2011) doi:10.1038/nn.2762
Published online, 20 March 2011.

Claire Jacob, Carlos N Christen, Jorge A Pereira, Christian Somandin, Arianna Baggiolini, Pirmin Lötscher, Murat Özçelik, Nicolas Tricaud, Dies Meijer, Teppei Yamaguchi, Patrick Matthias & Ueli Suter

In Schwann cells, HDAC1 and HDAC2 exert specific primary functions: HDAC2 activates the transcriptional program of myelination in synergy with Sox10, whereas HDAC1 controls Schwann cell survival.

Stem Cell Research May Lead To New Treatments For Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, Stroke, Spinal Cord Injury

Medical News Today, Article Date: 26 Mar 2011

As always, they forget the rare diseases, but I think this aproach is also useful for FA.

A group of scientists at Marshall University is conducting research that may someday lead to new treatments for repair of the central nervous system.

Price said the neurons they found appear to have many of the qualities desired for cells being used in development of therapies for slowly progressing, degenerative conditions

Multipotent progenitor cells derived from adult peripheral blood of swine have high neurogenic potential in vitro. Nadja Spitzer, Gregory S. Sammons, Heather M. Butts, Lawrence M. Grover, Elmer M. Price.Journal of Cellular Physiology, 2011; DOI: 10.1002/jcp.22670

Short-term low-frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain-derived neurotrophic factor on Schwann cell polarization

J Neurosci Res. 2010 Sep;88(12):2578-87.

Wan L, Zhang S, Xia R, Ding W.
Department of Anatomy, Medical College of Nanchang University, Nanchang 330006, China.

Keywords: Electrical stimulation (ES), nerve injuries, direct neurite outgrowth, peripheral remyelination, P0, Par-3, brain-derived neurotrophic factor (BDNF), dorsal root ganglion neuron/Schwann cell, 20-Hz ES, Schwann cell myelination.

Surgical treatment of neurological scoliosis using hybrid construct (lumbar transpedicular screws plus thoracic sublaminar acrylic loops).

Eur Spine J. 2011 Mar 15

La Rosa G, Giglio G, Oggiano L.
Department of Paediatric Surgery, Orthopaedic Unit, Research Institute Paediatric Hospital Bambino Gesù Palidoro, Fiumicino, Italy.

Keywords: segmental spine instrumentation, Cotrel-Dobousset (CD), sublaminar acrylic loops (Universal Clamp), spinal fixation implant, neurologic scoliosis, Socore TM spinal assembly, transpedicular lumbar screws, thoracic hooks, cerebral palsy, Friedreich ataxia, Aicardi syndrome, short operative time, low vascular and neurologic risks.

Cotrel-Dubousset instrumentation in neuromuscular scoliosis.

Eur Spine J. 2011 Mar 15.

Piazzolla A, Solarino G, De Giorgi S, Mori CM, Moretti L, De Giorgi G.

Dipartimento di Metodologia Clinica e Tecnologie Medico Chirurgiche, Università degli Studi di Bari, Bari, Italy.

Keywords: retrospective study, neuromuscular scoliosis (NMS), Spinal deformity, brace, surgery, solid spinal fusion, Cotrel-Dubousset (CD) surgical technique, Friedreich's ataxia, cerebral palsy, muscular dystrophy, polio, syringomyelia, spinal atrophy, kyphosis, lordosis.

Protein That Keeps Brain Signals Intact Yields Clue To Disorders

Medical News Today, Article Date: 14 Mar 2011

Researchers at the University of Edinburgh in the UK have found a new clue for understanding neurological disorders that occur when the brain can't send signals to other parts of the body.

Original paper:

"A Critical Role for Neurofascin in Regulating Action Potential Initiation through Maintenance of the Axon Initial Segment."
Barbara Zonta, Anne Desmazieres, Arianna Rinaldi, Steven Tait, Diane L. Sherman, Matthew F. Nolan, Peter J. Brophy.
Neuron, 10 March 2011 (Vol. 69, Issue 5, pp. 945-956).
DOI:10.1016/j.neuron.2011.02.021

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Mitochondria-Targeted Small Molecule Therapeutics and Probes

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

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.

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.
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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.

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,

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."

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

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

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"

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.

Brain diffusion-weighted imaging in Friedreich's ataxia

Mov Disord. 2011 Mar 2. doi: 10.1002/mds.23518.

Rizzo G, Tonon C, Valentino ML, Manners D, Fortuna F, Gellera C, Pini A, Ghezzo A, Baruzzi A, Testa C, Malucelli E, Barbiroli B, Carelli V, Lodi R.

MR Spectroscopy Unit, Department of Internal Medicine, Aging and Nephrology, University of Bologna, Bologna, Italy; Department of Neurological Sciences, University of Bologna, Bologna, Italy.

"The extent of neurodegeneration in FRDA appears more extended than previously reported."

Keywords: Friedreich ataxia (FRDA), brain damage in FRDA, in vivo markers of neurodegeneration, diffusion-weighted imaging (DWI), Axial DW images, mean diffusivity (MD) maps, medulla, pons, inferior, middle and superior cerebellar peduncles (ICP, SCP, MCP), dentate nucleus, cerebellar white matter, thalamus, caudate, putamen, pallidus, pyramidal tracts at level of posterior limb of internal capsule (PLIC), optic radiations (OR), and corpus callosum, Histograms of MD, International Cooperative Ataxia Rating Scale (ICARS).

Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task.

Brain Cogn. 2011 Feb 25

Corben LA, Akhlaghi H, Georgiou-Karistianis N, Bradshaw JL, Egan GF, Storey E, Churchyard AJ, Delatycki MB.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton 3800, Victoria, Australia.

KEYWORDS: Friedreich ataxia (FRDA), impairment in motor planning, cerebral cortex and/or cerebello-cortical projections, Simon interference task.

Human Basal Ganglia and the Dynamic Control of Force during On-Line Corrections

The Journal of Neuroscience, February 2, 2011, 31(5):1600-1605; doi:10.1523/JNEUROSCI.3301-10.2011

Scott T. Grafton1 and Eugene Tunik2

1Sage Center for the Study of Mind, Department of Psychology, University of California, Santa Barbara, California 93106, and 2Department of Rehabilitation and Movement Science, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07107

Keywords: Natural movements, submovements, basal ganglia, force amplitude, change, and duration, proprioceptive error, globus pallidus, subthalamic nucleus.