After ataxia withdrawal, Santhera considers strategic moves

After ataxia withdrawal, Santhera considers strategic moves. Santhera Pharmaceuticalsnews release,
February 28, 2013

What is the cost of rare diseases such as Friedreich's Ataxia?

What is the cost of rare diseases such as Friedreich's Ataxia?. Medical Xpress, February 27, 2013

What is the cost of rare diseases such as Friedreich's Ataxia? By analyzing direct and indirect costs of care research in BioMed Central's open access journal Orphanet Journal of Rare Diseases calculated that conservatively this rare disease costs between £11,000 and £19,000 per person per year. Proper understanding resource allocation is important in minimizing the effect of Friedreich's Ataxia on people's lives while maximizing their quality of life.

Impact of Friedreich's Ataxia on health-care resource utilization in the United Kingdom and Germany. Paola Giunti, Julia Greenfield, Alison J Stevenson, Michael H Parkinson, Jodie L Hartmann, Ruediger Sandtmann, James Piercy, Jamie O'Hara, Leo Ruiz Casas and Fiona M Smith, Orphanet Journal of Rare Diseases 2013, 8:38 doi:10.1186/1750-1172-8-38

Santhera to Discontinue Sale of Catena® in Canada

Santhera to Discontinue Sale of Catena® in Canada. 12:40 EST 27 Feb 2013 | Thomson Reuters.

Liestal, Switzerland, February 27, 2013 - Santhera Pharmaceuticals (SIX: SANN) announced today the voluntary withdrawal of Catena® from the Canadian market. This decision follows review of additional data from clinical trials in patients with Friedreich's Ataxia, and subsequent consultation with Health Canada.

Santera's web page

White House announces new US open access policy

White House announces new US open access policy. Newsblog (nature.com), 22 Feb 2013, Posted by Richard Van Noorden.

In a long-awaited leap forward for open access, the US government said today that publications from taxpayer-funded research should be made free to read after a year’s delay – expanding a policy which until now has only applied to biomedical science.

With both the US and Europe supporting delayed-access to publications, the UK government looks increasingly isolated in its preference for immediate open access. That policy is due to come in from 1 April, but the details are not yet clear. Communication around the policy was yesterday criticized as “unacceptable” by a House of Lords inquiry.

Very late-onset Friedreich ataxia: later than life expectancy?

Very late-onset Friedreich ataxia: later than life expectancy?. Vincent Alvarez, Pierre Arnold, Thierry Kuntzer; Journal of Neurology February 2013. DOI:10.1007/s00415-013-6874-6

Mitochondrial Transport, Metabolism and ROS Production in Disease Models

Mitochondrial Transport, Metabolism and ROS Production in Disease Models. Peter Hollenbeck, reearch talk in the Samuel Colella Lecture Series in Neurodegeneration at the Institute for Neurodegenerative Diseases of the University of Pittsburgh School of Medicine.


The talk covered studies from the Hollenbeck laboratory on the etiology of Friedreich ataxia and Parkinson’s disease. The work implicates defects in axonal transport, metabolism and mitochondrial turnover in the death of neurons.

Job opportunity. Study of the role of glial cells and neurons-glia interactions in Alzheimer disease and Friedreich ataxia

Job opportunity. Study of the role of glial cells and neurons-glia interactions in Alzheimer disease and Friedreich ataxia.  UNIVERSITE PARIS

Identification of physiopathological mechanisms in human degenerative pathologies and new therapeutic compounds using Drosophila and mice. Study of the role of glial cells and neurons-glia interactions in Alzheimer disease and Friedreich ataxia using approaches from genetics to behavioral studies

Discovery in HIV May Solve Efficiency Problems for Gene Therapy

Discovery in HIV May Solve Efficiency Problems for Gene Therapy. Case Western Reserve University (2013, February 14). Discovery in HIV may solve efficiency problems for gene therapy.

Journal Reference:

Mastooreh Chamanian, Katarzyna J. Purzycka, Paul T. Wille, Janice S. Ha, David McDonald, Yong Gao, Stuart F.J. Le Grice, Eric J. Arts. A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal Frameshifting to Selective Viral RNA Encapsidation. Cell Host & Microbe, 2013; 13 (2): 181 DOI: 10.1016/j.chom.2013.01.007

“Generación de Un Modelo Experimental Humano de Ataxia de Friedreich Mediante Células Troncales Pluripotentes Inducidas (Ipsc)”

“Generación de Un Modelo Experimental Humano de Ataxia de Friedreich Mediante Células Troncales Pluripotentes Inducidas (Ipsc)”. "Offer of employment"

El proyecto “Generación de Un Modelo Experimental Humano de Ataxia de Friedreich Mediante Células Troncales Pluripotentes Inducidas (Ipsc)” es un proyecto financiado a través de la convocatoria de la Consejería de Salud y Bienestar Social del año 2010, con número de expediente 726/2010.

Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy

Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy. Chiranjeevi Sandi, Sahar Al-Mahdawi, and Mark A. Pook. Genetics Research International, Volume 2013 (2013), Article ID 852080, 12 pages. http://dx.doi.org/10.1155/2013/852080

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Friedreich's Ataxia

Friedreich's Ataxia. P.E. Hart, A.H.V. Schapira, Encyclopedia of Biological Chemistry, 2013, Pages 332-334. http://dx.doi.org/10.1016/B978-0-12-378630-2.00443-6.

Keywords: Friedreich's ataxia (FRDA), ataxia, sensory loss, cardiomyopathy, skeletal abnormalities, diabetes, optic atrophy, frataxin, neurodegenerative disorder.

Pharmacological Screening Using an FXN-EGFP Cellular Genomic Reporter Assay for the Therapy of Friedreich Ataxia

Pharmacological Screening Using an FXN-EGFP Cellular Genomic Reporter Assay for the Therapy of Friedreich Ataxia. Lingli Li, Lucille Voullaire, Chiranjeevi Sandi, Mark A. Pook, Panos A. Ioannou, Martin B. Delatycki, Joseph P. Sarsero. PLoS ONE 8(2): e55940. doi:10.1371/journal.pone.0055940 (2013)

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Abstract

Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.

Phase 2 clinical trials with OX1 (VP 20629) in patients with Friedreich's Ataxia

Phase 2 clinical trials with OX1 (VP 20629) in patients with Friedreich's Ataxia. Intellect Neurosciences Issues Letter to Shareholders, 02/13/2013 GlobeNewswire

An important event to anticipate in 2013 is the initiation of Phase 2 clinical trials with OX1 (VP 20629) in patients with Friedreich's Ataxia ("FA"), which we expect to occur mid-year based on statements Vincent Milano, CEO of ViroPharma, made during his presentation at the JP Morgan Health Care Conference in January. ViroPharma intends to file for Orphan Drug Designation upon review of the Phase 2 proof-of-concept data. February 28 marks the sixth international Rare Disease Day in 24 European countries. We are pleased ViroPharma is collaborating with FARA (Friedreich's Ataxia Research Alliance) to raise awareness about FA and Rare Disease through the media. Intellect helped forge the alliance between ViroPharma and FARA and we are proud of our role in developing OX1 and highlighting its potential for FA.

Cognition in Late-Onset Friedreich Ataxia.

Cognition in Late-Onset Friedreich Ataxia. Nieto A, Correia R, de Nóbrega E, Montón F, Barroso J.; Cerebellum. 2013 Feb 9. DOI 10.1007/s12311-013-0457-z.

Keywords: Friedreich ataxia (FRDA), Friedreich ataxia-LOFA, processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language.

Australian families living with rare disease: experiences of diagnosis, health services use and needs for psychosocial support

Australian families living with rare disease: experiences of diagnosis, health services use and needs for psychosocial support. Matilda Anderson, Elizabeth J Elliott, Yvonne A Zurynski, Orphanet Journal of Rare Diseases 2013, 8:22 doi:10.1186/1750-1172-8-22. Published: 11 February 2013.

Families of children living with a rare disease report significant health and social burden, however, few studies have systematically examined family needs by using validated tools to assess the scope and extent of this burden. Our aim was to develop a comprehensive survey to assess health, psychosocial and financial impacts on Australian families caring for a child with a rare disease.

Australian families caring for children with genetic metabolic disorders are adversely impacted by delays in diagnosis, lack of easy access to peer support groups and lack of psychological support. Further research is needed to estimate economic impact and to analyse health service delivery models for children with rare diseases in Australia.

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Review about ataxias

ATAXIA, Dr. M. Yasser Metwally, Professor of neurology, Ain Shams university, Cairo, Egypt

Interesting paper about ataxia diagnosis. The site also contains extensive information on neurology, diagnostic imaging, etc.

Friedreich's ataxia pg 21-28

Site: http://yassermetwally.com/

Scientists Find Way to Knockup Genes

Scientists Find Way to Knockup Genes. PR Newswire, CAMBRIDGE, England, Jan. 31, 2013 /PRNewswire/

"In many ways, the technique is the opposite of RNAi"

Italian scientists use molecular RNA Chaperones to increase protein production from individual genes. The technique is being hailed as a breakthrough in biotechnology that will transform cell science, accelerating the development of new medicines.

A non-coding RNA specifically binds to messenger RNA (mRNA) from the target gene. It then acts as a chaperone, efficiently escorting the target mRNA to ribosomes, where proteins are made.

Upregulation of the Mitochondrial Lon Protease Allows Adaptation to Acute Oxidative Stress but Dysregulation is Associated with Chronic Stress, Disease, and Aging

Upregulation of the Mitochondrial Lon Protease Allows Adaptation to Acute Oxidative Stress but Dysregulation is Associated with Chronic Stress, Disease, and Aging. Jenny K. Ngo, Laura C.D. Pomatto, Kelvin J.A. Davies. Redox Biology, Available online 9 February 2013. http://dx.doi.org/10.1016/j.redox.2013.01.015.

Keywords: Adaptation, Hormesis, Lon Protease, Protein Degradation and Oxidation, Mitochondria, Oxidative Stress.


In a Friedreich Ataxia mouse model, in which frataxin has been deleted in striated muscles, an increase in ClpP and Lon mRNA, protein, and activity was observed in the isolated mitochondria of mice between 5 and 10 weeks of age [55]. The upregulation of Lon and ClpP was accompanied by a progressive loss of mitochondrial Fe-S proteins with no change in mRNA levels, suggesting degradation.

See also: Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins

The Gait Variability Index: A new way to quantify fluctuation magnitude of spatiotemporal parameters during gait

The Gait Variability Index: A new way to quantify fluctuation magnitude of spatiotemporal parameters during gait. Arnaud Gouelle, Fabrice Mégrot, Ana Presedo, Isabelle Husson, Alain Yelnik, Georges-François Penneçot. Gait & Posture, Available online 8 February 2013. http://dx.doi.org/10.1016/j.gaitpost.2013.01.013

Keywords: Gait variability, Fluctuation magnitude, Spatiotemporal parameters, Friedreich's Ataxia

Hypoxia inducible factor prolyl hydroxylases as targets for neuroprotection by “antioxidant” metal chelators: From ferroptosis to stroke

Hypoxia inducible factor prolyl hydroxylases as targets for neuroprotection by “antioxidant” metal chelators: From ferroptosis to stroke. Rachel E. Speer, Saravanan S. Karuppagounder, Manuela Basso, Sama Sleiman, Amit Kumar, David Brand, Natalya Smirnova, Irina Gazaryan, Soah J. Khim, Rajiv R. Ratan. Free Radical Biology and Medicine, Available online 31 January 2013. http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.026

Keywords: Metal chelators, Neurodegeneration, Hypoxia inducible factors, Transcription, Prolyl hydroxylases.

See also:
Frataxin participates to the hypoxia-induced response in tumors
Neuroprotective Multifunctional Iron Chelators: From Redox-Sensitive Process to Novel Therapeutic Opportunities

Mesenchymal stem cells exert a remarkable regenerative effect requiring minimal CNS integration

Mesenchymal stem cells exert a remarkable regenerative effect requiring minimal CNS integration. Antonio Uccelli, Experimental Neurology, Available online 4 February 2013.

The concept of repair of the nervous system by adult stem cells has recently evolved from the original hypothesis that tissue regeneration could have been achieved through stem cells differentiation into neural cells to the current vision that they act mainly by means of paracrine mechanisms. Is preferable the stem cells transplantation or the administration of their secreted factors?.

Keywords: Mesenchymal stem cells, microglia, chemokines, neuroprotection, immunomodulation

The epidemiology of intermittent and chronic ataxia in children in Manitoba, Canada

The epidemiology of intermittent and chronic ataxia in children in Manitoba, Canada. Michael S Salman, Esther J Lee, Anindita Tjahjadi and Bernard N Chodirker. Developmental Medicine & Child Neurology, Article first published online: 7 FEB 2013 | DOI: 10.1111/dmcn.12081

Keywords: retrospective study, age 0–16y, from 1991 to 2008, 184 patients, Angelman syndrome (n=16), ataxia telangiectasia (n=13), mitochondrial disease (n=9), Friedreich ataxia (n=7), stroke (n=7), familial/genetic episodic ataxia (n=7).

The Reciprocal Cerebellar Circuitry in Human Hereditary Ataxia.

The Reciprocal Cerebellar Circuitry in Human Hereditary Ataxia. Koeppen AH, Ramirez RL, Bjork ST, Bauer P, Feustel PJ.. Cerebellum. 2013 Feb 7. [Epub ahead of print].

Keywords: spinocerebellar ataxias (SCA), Friedreich's ataxia (FRDA), central and peripheral nervous systems, "reciprocal cerebellar circuitry", Purkinje cells, dentate nuclei (DN), inferior olivary nuclei (ION).

Orthobullets: Friedreich's Ataxia

Friedreich's Ataxia, orthobullets.
Author: Derek Moore MD,