A gene expression phenotype in lymphocytes from Friedreich's Ataxia patients

Annals of Neurology, DOI: 10.1002/ana.22526

Giovanni Coppola MD, Ryan Burnett PhD, Susan Perlman MD, Revital Versano,Fuying Gao, Heather Plasterer PhD, Myriam Rai PhD, Francesco Saccá MD, Alessandro Filla MD, David R. Lynch MD PhD, James R. Rusche PhD, Joel M. Gottesfeld PhD, Massimo Pandolfo MD, Daniel H. Geschwind MD PhD.

Keywords: Biomarker; Gene expression; Friedreich's ataxia; Therapy

6th International Conference on Fe‐S Protein Biogenesis and Regulation

6th International Conference on
Fe‐S Protein Biogenesis and Regulation
22 – 25 August 2011 in Cambridge, UK

The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity?

Neuroscience, doi:10.1016/j.neuroscience.2011.06.057, Available online 25 June 2011.

Louise A. Corben 1, 2, Nellie Georgiou-Karistianis 2, John L. Bradshaw 2, Darren R. Hocking 3, Andrew J. Churchyard 4 and Martin B. Delatycki 1, 5, 6

1 Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
2 Experimental Neuropsychology Research Unit, School of Psychology and, Psychiatry, Monash University, Clayton, Victoria, Australia
3 Developmental Neuroscience and Genetic Disorders Laboratory, School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia
4 Monash Neurology, Monash Medical Centre, Clayton, Victoria, Australia
5 Department of Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia
6 Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

KEYWORDS: Friedreich ataxia (FRDA), cognitive and/or psychomotor capacity, cerebellum, cortex, Fitts’ Law, preplanning of movement, online error detection and correction, prefrontal/anterior regions.

Case Report : Massive uterine leiomyoma in a patient with Friedreich’s ataxia: Is there a possible association?

Case Reports in Medicine, Received 26 May 2011; Accepted 24 June 2011

Evangelos Misiakos, Elli Siama, Dimitrios Schizas, Constantinos Petropoulos, Nick Zavras, Nikos Economopoulos, Alexandros Charalabopoulos, and Anastasios N. Macheras
University of Athens School of Medicine, Athens, Greece.

KEYWORDS: Friedreich’s ataxia, leiomyoma, intestinal obstruction, tumor excision, adhesionlysis, "neoplasms uncommon for their young age".

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Echocardiography: A Requisite Friend of the Cardiac Geneticist

Journal of the American Society of Echocardiography
Volume 24, Issue 7 , Pages 790-791, July 2011

Keywords: role of echocardiography in the early detection, frataxin, Friedreich's ataxia, noninvasive application.

To Be Targeted: Is the Magic Bullet Concept a Viable Option for Synthetic Nucleic Acid Therapeutics?

Human Gene Therapy. Ahead of print. doi:10.1089/hum.2011.065.

Manfred Ogris and Ernst Wagner.
Pharmaceutical Biotechnology, Ludwig Maximilians University, Munich 81377, Germany.

Keywords: Nucleic acids, genetic disorders, infectious diseases, cancer, viral vectors, synthetic delivery systems, receptor targeting of synthetic vectors, improve the specificity, increase the efficiency of nucleic acid delivery.

Correlation of frataxin content in blood and skeletal muscle endorses frataxin as a biomarker in Friedreich ataxia

Movement Disorders, 26: n/a. doi: 10.1002/mds.23789
Article first published online: 20 JUN 2011

Nachbauer, W., Wanschitz, J., Steinkellner, H., Eigentler, A., Sturm, B., Hufler, K., Scheiber-Mojdehkar, B., Poewe, W., Reindl, M. and Boesch, S

Keywords: Friedreich ataxia; frataxin; skeletal muscle; erythropoietin

Brain Implant Uses The Body's Skin Like A Conductor To Wirelessly Transmit The Brain's Neural Signals To Control A Computer

Medical News Today, Article Date: 17 Jun 2011
A brain implant developed at the University of Michigan uses the body's skin like a conductor to wirelessly transmit the brain's neural signals to control a computer, and may eventually be used to reactivate paralyzed limbs. Read more ....

Pricing and reimbursement of orphan drugs: the need for more transparency

Steven Simoens
Orphanet Journal of Rare Diseases 2011, 6:42doi:10.1186/1750-1172-6-42
Published: 17 June 2011

OPEN ACCES

Abstract (provisional)

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.

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Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Hum Brain Mapp. 2011 Jun 14. doi: 10.1002/hbm.21319. [Epub ahead of print]

Ginestroni A, Diciotti S, Cecchi P, Pesaresi I, Tessa C, Giannelli M, Nave RD, Salvatore E, Salvi F, Dotti MT, Piacentini S, Soricelli A, Cosottini M, De Stefano N, Mascalchi M.
Department of Clinical Physiopathology, Radiodiagnostic Section, University of Florence, Florence, Italy.

Keywords: Friedreich's ataxia (FRDA), neurodegeneration, spinal cord, brain, MR Imaging (fMRI), left primary sensory-motor cortex, right cerebellum, left thalamus, right dorsolateral prefrontal cortex, globus pallidus, anterior cingulum, globus pallidus, regional neuronal damage, compensatory significance.

Friedreich’s ataxia variants I154F and W155R diminish frataxin-based activation of the iron-sulfur cluster assembly complex

Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi200666h
Publication Date (Web): June 14, 2011

Chi-Lin Tsai , Jennifer Bridwell-Rabb , and David P. Barondeau

Keywords: Friedreich’s ataxia (FRDA), frataxin (Fxn), GAA expansion, missense mutation, FRDA I154F, W155R variants, Nfs1, Isd11, Isu2, Fe-S cluster assembly machine, Fxn triggers sulfur transfer from Nfs1 to Isu.

New project: Identification of the E3 ligase that ubiquitinates frataxin

Principal researcher: Dr Roberto Testi, Department of Experimental Medicine,
University of Rome, ‘Tor Vergata,’ Italy

Keywods: frataxin, ubiquitin-proteasome system, ubiquitination, E3 ligase.

Sherman ku PhD working with friedreich's ataxia and induced pluripotent stem cells (iPSC)

Sigma bioblogs (3 Jun 2011)
Sherman Ku PhD interview
The Scripps Research Institute, Member of the Gottesfeld Lab

What is the focus of your research?
My research has focused on developing an induced pluripotent stem cell (iPSC) model of Friedreich’s ataxia (FRDA), which is ..... read more....

Edison Pharmaceuticals Announces Results of EPI-A0001 Phase 2A Double Blind Placebo Controlled 28-Day Clinical Trial in the Mitochondrial Disease- Friedreich's Ataxia

10th of June 2011

MOUNTAIN VIEW, Calif., June 10, 2011 /PRNewswire/ -- Edison Pharmaceuticals, Inc. announced today preliminary results obtained on a 28-day phase 2A clinical trial in Friedreich's ataxia.

EPI-A0001 did significantly improve neurological function as assessed by the Friedreich's Ataxia Rating Scale (FARS).

Read more

Emergency Use Protocol for EPI-743 in Acutely Ill Patients With Inherited Mitochondrial Respiratory Chain Disease Within 90 Days of End-of-Life Care

This study is currently recruiting participants.

First Received on June 7, 2011. Last Updated on June 9, 2011
Sponsor: Edison Pharmaceuticals Inc
Information provided by: Edison Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT01370447


Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Transcranial Sonography Reveals Cerebellar, Nigral, and Forebrain Abnormalities in Friedreich’s Ataxia

Neurodegenerative Dis, (DOI: 10.1159/000327751)

Matthis Synofzik, Jana Godau, Tobias Lindig, Ludger Schöls, Daniela Berg
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and German Research Center for Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany

Keywords: Ataxia, Transcranial sonography, Friedreich’s ataxia, Imaging, Substantia nigra, Dentate nucleus, Iron, Cerebellum

Mortality in Friedreich Ataxia

Journal of the Neurological Sciences,Article in Press,
doi:10.1016/j.jns.2011.05.023

(J Neurol Sci. 2011 Aug 15;307(1-2):46-9. Epub 2011 Jun 8.)

Amy Y. Tsoua, Erin K. Paulsena, b, c, d, Sarah J. Lagedrosta, b, c, d, Susan L. Perlmane, Katherine D. Mathewsf, George R. Wilmotg, Bernard Ravinah, Arnulf H. Koeppeni, j and David R. Lyncha, b, c, d,

a Department of Neurology, University of Pennsylvania Medical School, United States
b Department of Pediatrics, University of Pennsylvania Medical School, United States
c Children's Hospital of Philadelphia, United States
d University of Pennsylvania Medical School, United States
e University of California Los Angeles, Los Angeles, CA, United States
f University of Iowa, Iowa City, IA, United States
g Emory University, Atlanta, GA, United States
h University of Rochester, Rochester, NY, United States
i VA Hospital, Albany, NY, United States

Keywords: Cerebellum; Sensory; Cardiomyopathy; Echocardiogram; Arrhythmia; Neurodegenerative disease

Repligen Reports Fourth Quarter ........ "RG2833 for Friedreich’s Ataxia"

9th of June 2011

RG2833 for Friedreich’s Ataxia
We are currently developing histone deacetylase class 1 inhibitors for the treatment of inherited neurodegenerative diseases such as Friedreich's ataxia. Friedreich's ataxia is caused by inadequate production of the protein frataxin which leads to degeneration of the nerves controlling muscle movements. Pending regulatory approval, we plan to initiate a Phase 1 study of RG2833 in Friedreich's ataxia patients in Europe by the end of the year. We are currently engaged in discussions with potential
pharmaceutical partners to evaluate whether partnering this program would increase the trajectory for global development and ultimately maximize the commercial potential of the asset.

Stem Cell Transplantation Offers 'Sea Of Opportunity' For Treating Debilitating Diseases

Medical News Today, Article Date: 09 Jun 2011

An article in the current issue of Technology & Innovation, Proceedings of the National Academy of Inventors ™ reports on the bright future and enormous need for stem cell therapeutics that may offer hope for those suffering from debilitating and deadly diseases. read more...

Edison Pharmaceuticals Announces FDA Grants EPI-743 Orphan Drug Designation

Medical News Today, Article Date: 09 Jun 2011

Edison Pharmaceuticals, Inc. announced the United States Food and Drug Administration has granted orphan drug designation to EPI-743 for treatment of inherited mitochondrial respiratory chain diseases. read more

Edison Pharmaceuticals ofrecerá un acceso ampliado al EPI-743 para la enfermedad mitocondrial

MOUNTAIN VIEW, California, 8 de junio de 2011 /PRNewswire/

La FDA autorizó un Programa de Acceso Ampliado con el propósito de administrar el fármaco en fase de investigación EPI-743 a los pacientes graves diagnosticados con enfermedades mitocondriales heredadas de la cadena respiratoria. leer más...

Edison Pharmaceuticals to Provide Expanded Access to EPI-743 for Mitochondrial Disease

7th of June 2011, Source: PR Newswire

MOUNTAIN VIEW, Calif., June 8, 2011 /PRNewswire/ -- Edison Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) has allowed an Expanded Access program to provide EPI-743 to seriously ill patients diagnosed with inherited respiratory chain diseases of the mitochondria. read more

Edison Pharmaceuticals élargit l'accès à EPI-743 pour les maladies mitochondriales

MOUNTAIN VIEW, Californie, June 8, 2011 /PRNewswire/ --

- La FDA autorise l'utilisation d'un nouveau médicament expérimental pour les cas menaçant le pronostic vital

Edison Pharmaceuticals, Inc. a aujourd'hui annoncé que la "Food and Drug Administration" américaine (la FDA) a autorisé un programme d'accès élargi pour offrir EPI-743 aux patients gravement malades ayant reçu un diagnostic de maladies héréditaires de la chaîne respiratoire mitochondriale. Les patients dont la maladie a été génétiquement confirmée comme ceux qui répondent à certains critères cliniques, en l'absence de confirmation génétique, sont tous éligibles. Lire plus.......

Edison Pharmaceuticals sorgt für erweiterten Zugang zu EPI-743 für mitochondriale Erkrankungen

MOUNTAIN VIEW, Kalifornien, June 8, 2011 /PRNewswire/ --

- FDA genehmigt Anwendung von Medikament in klinischer Testphase (Investigational New Drug) bei lebensbedrohlichen Befunden

Edison Pharmaceuticals, Inc. gab heute bekannt, dass die amerikanische Zulassungsbehörde für Lebens- und Arzneimittel, die US Food and Drug Administration (FDA), ein sogenanntes Expanded-Access-Programm genehmigt hat, durch das EPI-743 an schwerkranke Patienten mit diagnostizierter Störung der Atmungskette aufgrund mitochondrialer Erbkrankheiten verabreicht werden darf. Darunter fallen sowohl Patienten mit genetisch bestätigter Krankheit als auch Patienten, die bei fehlender genetischer Bestätigung spezifische klinische Kriterien erfüllen. Lesen Sie mehr ...

Differential Expression of PGC-1α and Metabolic Sensors Suggest Age-Dependent Induction of Mitochondrial Biogenesis in Friedreich Ataxia Fibroblasts

2011 PLoS ONE 6(6): e20666. doi:10.1371/journal.pone.0020666, OPEN ACCESS

García-Giménez JL, Gimeno A, Gonzalez-Cabo P, Dasí F, Bolinches-Amorós A, et al.

The induction of mitochondrial biogenesis in FRDA may be a consequence of the mitochondrial impairment associated with disease evolution. The increase of ROS and the involvement of the oxidative phosphorylation may be an early event in the cell pathophysiology of frataxin deficiency, whereas increase of mitochondriogenic response might be a later phenomenon associated to the individual age and natural history of the disease, being more evident as the patient age increases and disease evolves. This is a possible explanation of heart disease in FRDA.

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Clinical trials for stem cell therapies

BMC Medicine 2011, 9:52doi:10.1186/1741-7015-9-52
OPEN ACCESS

Alan Trounson, Rahul G Thakar, Geoff Lomax and Don Gibbons.
California Institute for Regenerative Medicine, San Francisco, USA

In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun.

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Characterization of poly (rc) binding protein (pcbp2) and frataxin

Wayne State University Theses. Paper 71.

Ghimire-Rijal, Sudipa, (2011). Wayne State University Theses. Paper 71.

Keywords: Iron, cofactor, cellular iron homeostasis, Poly (rC) Binding Protein family, iron chaperone, PCBP2, dimeric protein.

The cerebellar component of Friedreich's ataxia.

Acta Neuropathol. 2011 Jun 3. [Epub ahead of print]

Koeppen AH, Davis AN, Morral JA.
Research Service (151), Veterans Affairs Medical Center, USA

Keywords: frataxin, Friedreich's ataxia (FRDA),progressive atrophy, dentate nucleus (DN), intact Purkinje cell somata, dendrites, severe loss of large NSE-reactive neurons, Small neurons remained intact, basket fibers, Golgi neurons, Golgi axonal plexuses, γ-aminobutyric acid (GABA), GABA-ergic terminals.

Utilisation of Advance Motor Information is Impaired in Friedreich Ataxia.

Cerebellum. 2011 Jun 2. [Epub ahead of print]

Corben LA, Delatycki MB, Bradshaw JL, Churchyard AJ, Georgiou-Karistianis N.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.

Keywords: Friedreich ataxia (FRDA), motor planning ability, age of disease onset, motor cognition, cerebellar impairment, cerebro-ponto-cerebello-thalamo-cerebral loops, direct primary cortical pathology.

Milestones in ataxia.

Mov Disord. 2011 May;26(6):1134-41. doi: 10.1002/mds.23559.

Klockgether T, Paulson H.

Department of Neurology, University Hospital Bonn, Bonn, Germany; German Center for Neurodegenerative Disorder (DZNE), Bonn, Germany

Keywords: genetic and molecular basis of ataxias, pathogenesis, spinocerebellar ataxias, ataxia telangiectasia, Friedreich ataxia, protein aggregation, failure of protein homeostasis, perturbations in ion channel function, defects in DNA repair, mitochondrial dysfunction.