Aliança internacional d’afectats per l’atàxia de Friedreich per finançar el projecte de teràpia gènica desenvolupat a Espanya

Aliança internacional d’afectats per l’atàxia de Friedreich per finançar el projecte de teràpia gènica desenvolupat a Espanya.

Científics de l’Institut de Recerca Biomèdica (IRB) i el Centre de Biologia Molecular Severo Ochoa (CBMSO) van iniciar el projecte dos mesos enrere.

El projecte és fruit de la iniciativa d’afectats espanyols units en la plataforma Genefa en col·laboració amb la Federació d’Atàxies d’Espanya i BabelFAmily. Ara, s’hi suma The Friedreich's Ataxia Research Alliance (FARA), una de les principals organitzacions de pacients dels Estats Units.

L’aportació de FARA suposa el 50% del pressupost total de 300.000€ del projecte. Els fons de FARA provenen del suport de les famílies dels pacients i comunitats afins dels EUA, i d'altres agents internacionals com FARA-Irlanda.

FARA (Friedreich's Ataxia Research Aliance) Press Release
Notícies IRB Barcelona

Alianza internacional de afectados por la ataxia de Friedreich para financiar el proyecto de terapia génica desarrollado en España

Alianza internacional de afectados por la ataxia de Friedreich para financiar el proyecto de terapia génica desarrollado en España 28 de Enero 2014.

Científicos del Instituto de Investigación Biomédica (IRB) y el Centro de Biología Molecular Severo Ochoa (CBMSO) iniciaron el proyecto dos meses atrás.

El proyecto es fruto de la iniciativa de afectados españoles unidos en la plataforma Genefa en colaboración con la Federación de Ataxias de España y BabelFAmily. Ahora, se suma The Friedreich's Ataxia Research Alliance (FARA), una de las principales organizaciones de pacientes de los Estados Unidos.

La aportación de FARA supone el 50% del presupuesto total de 300.000€ del proyecto. Los fondos de FARA provienen del apoyo de las familias de los pacientes y comunidades afines de los EEUU y otros agentes internacionales como FARA-Irlanda.

FARA (Friedreich's Ataxia Research Aliance) Press release
Noticias IRB Barcelona

International patient advocates partner to fund Spanish gene-therapy project to treat Friedreich's ataxia

International patient advocates partner to fund Spanish gene-therapy project to treat Friedreich's ataxia

January 28, 2014

Scientists at the Institute for Research in Biomedicine (IRB) and the “Centro de Biología Molecular Severo Ochoa” (CBMSO) launched the project two months ago.

The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.

The support provided by FARA will account for 50% of the project budget of 300,000 euros. Of note, FARA’s funds come from the support of patient families and communities raising funds at a grassroots level and from other International advocates such as FARA – Ireland.

FARA (Friedreich's Ataxia Research Aliance) Press Release
IRB (Institute for Research in Biomedicine) Press Release

FXN GAA repeat expansions in amyotrophic lateral sclerosis

FXN GAA repeat expansions in amyotrophic lateral sclerosis. Naji Rizik, Axel Freischmidt, Albert C. Ludolph, Jochen H. Weishaupt; ournal of Clinical Neuroscience, Available online 27 January 2014. http://dx.doi.org/10.1016/j.jocn.2013.10.029

When homozygously present, an increased number of GAA repeats in the FXN gene results in a severely decreased expression of frataxin, resulting in the manifestation of FRDA. However, even heterozygous expansion of the trinucleotide repeat substantially reduces frataxin expression. Heterozygous expansion carriers are usually normal, but still display an increased risk for pathological glucose tolerance and, thus suggesting that a heterozygous FXN mutation leads to a borderline impairment of specific cell types at risk.

Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia

Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia. Eric C Deutsch, Devin Oglesbee, Nathaniel R Greeley, David R Lynch; J Neurol Neurosurg Psychiatry jnnp-2013-306788Published Online First: 24 January 2014 doi:10.1136/jnnp-2013-306788

Keywords: Frataxin measurements, peripheral tissues, patients, carriers.

Urinary Symptoms and Urodynamics Findings in Patients with Friedreich's Ataxia.

Urinary Symptoms and Urodynamics Findings in Patients with Friedreich's Ataxia. Musegante AF, Almeida PN, Monteiro RT, Barroso U Jr.; Int Braz J Urol. 2013 Nov-Dec;39(6):867-74. doi: 10.1590/S1677-5538.IBJU.2013.06.14

Keywords: LUTS, urinary tract and urodynamics changes, urinary symptoms, Urgency.

Synthetic Analogues of Redox-Enabled Natural Products

Synthetic Analogues of Redox-Enabled Natural Products . Fash, David Michael, Department of Chemistry, University of Virginia; Doctoral Dissertation.

Keywords: Dysfunctional mitochondria, reactive oxygen species (ROS), novel quinone analogues, idebenone analogues, -Tocopherol quinone derivatives, Friedreich’s ataxia.

Comparative (Computational) Analysis of the DNA Methylation Status of Trinucleotide Repeat Expansion Diseases

Comparative (Computational) Analysis of the DNA Methylation Status of Trinucleotide Repeat Expansion Diseases. Mohammadmersad Ghorbani, Simon J. E. Taylor, Mark A. Pook, and Annette Payne; Journal of Nucleic Acids, Volume 2013 (2013), Article ID 689798, 9 pages. http://dx.doi.org/10.1155/2013/689798

Full Text, Open access

Mitochondrial iron–sulfur protein biogenesis and human disease

Mitochondrial iron–sulfur protein biogenesis and human disease; Oliver Stehling, Claudia Wilbrecht, Roland Lill; Biochimie, Available online 23 January 2014. http://dx.doi.org/10.1016/j.biochi.2014.01.010

Keywords:Iron–sulfur cluster; Mitochondrial ISC system; Iron regulation; Genome integrity

Anaesthesia for orphan disease: combined spinal-epidural anaesthesia in a patient with Friedreich's ataxia

Anaesthesia for orphan disease: combined spinal-epidural anaesthesia in a patient with Friedreich's ataxia. Huercio, Iván; Guasch, Emilia; Brogly, Nicolas; Gilsanz, Fernando; European Journal of Anaesthesiology, January 21, 2014 - Volume Publish Ahead of Print - Issue - ppg
doi: 10.1097/EJA.0000000000000041

Optimizing Mouse Models of Neurodegenerative Disorders

Optimizing Mouse Models of Neurodegenerative Disorders. Future Neurology. Cathleen M Lutz, Melissa A Osborne; Future Neurology. 2014;9(1):67-75.

This experience in SMA raises interesting questions for FRDA. Does such a threshold also exist in FRDA models, where no or too low frataxin results in embryonic lethality, but levels of 10% or more result in mice that are phenotypcially normal? Can mice simply tolerate low levels of frataxin? Alternatively, perhaps FRDA is not just a disease of low frataxin protein, but insread is one in which the GAA repeat itself plays a greater role in the disease course, beyond just inhibiting transcription. Would mouse models of higher repeat length or uninterupted repeats produce a more robust phenotype? Additional FRDA models are desperately needed in order to help address these questions.

Repligen Announces Asset Purchase Agreement With BioMarin for HDACi Portfolio

Repligen Announces Asset Purchase Agreement With BioMarin for HDACi Portfolio. Company Release - 01/21/2014 07:30. WALTHAM, Mass., Jan. 21, 2014 (GLOBE NEWSWIRE)

Repligen Corporation announced today that it has entered into an asset purchase agreement with BioMarin Pharmaceutical Inc. ("BioMarin") to advance Repligen's histone deacetylase inhibitor (HDACi) portfolio. Includes Preclinical Compounds for Potential Treatment of Friedreich's Ataxia

Mammalian Fe–S cluster biogenesis and its implication in disease

Mammalian Fe–S cluster biogenesis and its implication in disease. Lena K. Beilschmidt, Hélène M. Puccio; Biochimie, Available online 16 January 2014. http://dx.doi.org/10.1016/j.biochi.2014.01.009

Keywords: Mitochondria; Iron–sulfur cluster; Genetic disease; Mutation.

A new technic for segmental spinal osteosynthesis using the posterior approach

A new technic for segmental spinal osteosynthesis using the posterior approach . Y. Cotrel, J. Dubousset; Orthopaedics & Traumatology: Surgery & Research, Available online 18 January 2014.DOI http://dx.doi.org/10.1016/j.otsr.2013.12.009

Full text pdf

Frataxin-bypassing Isu1: characterization of the bypass activity in cells and mitochondria

Frataxin-bypassing Isu1: characterization of the bypass activity in cells and mitochondria Yoon H, Knight SA, Pandey A, Pain J, Zhang Y, Pain D, Dancis A
The Biochemical Journal [2014].

Keywords: Frataxin, Fe-S cluster assembly, mitochondria, Isu scaffold proteins, heme proteins, iron homeostasis.

Production and application of polyclonal antibody against mouse frataxin

Production and application of polyclonal antibody against mouse frataxin. Hao S, Xu F, Li K.; (Chinese journal of biotechnology) Sheng Wu Gong Cheng Xue Bao. 2013 Sep;29(9):1313-22.

In a previous work showed that tissue-specific expression of FXN in cerebellum and heart generates two novel isoforms, This work provides a powerful tool for further research on mouse Fxn isoforms.

Beyond loss of frataxin: the complex molecular pathology of Friedreich ataxia

Beyond loss of frataxin: the complex molecular pathology of Friedreich ataxia; Evans-Galea MV, Lockhart PJ, Galea CA, Hannan AJ, Delatycki MB, Discovery Medicine [2014, 17(91):25-35]

A review about diverse array of molecular events that have been shown to influence clinical outcome in FRDA. The authors also examine additional pathogenic factors from other trinucleotide repeat diseases which could be potentially important in FRDA.

A Phase IIa Trial to Test Safety and Efficacy Interferon Gamma Treatment in Elevating Frataxin Levels in FRDA Patients

A Phase IIa Trial to Test Safety and Efficacy Interferon Gamma Treatment in Elevating Frataxin Levels in FRDA Patients. ClinicalTrials.gov

Sponsor: Azienda Policlinico Umberto I

The primary objective of this study is to investigate whether the treatment with IFN gamma can induce significant accumulation of frataxin in FRDA patients, a possibility suggested by pre-clinical evidence in an animal model of the disease.

Detailed Description:
This is a Phase 2 clinical trial. A total of 10 FRDA patients will be recruited All subjects will be treated with a dose of 100-150-200-micrograms of IFN gamma 1b (Imukin®) subcutaneously, with an interval of 14 days, for a total of 3 injections.

Anesthetic Management on a Patient with Friedreich’s Ataxia

Anesthetic Management on a Patient with Friedreich’s Ataxia. Ozgul U, Erdogan MA, Aydogan MS, Korkmaz MF, Nakir H, Durmus M.; Med-Science. 2013; 2(4): 928-34. doi:10.5455/medscience.2013.02.8083

Key words: Friedreich’s ataxia, Anesthesia, spinal fusion

Role of Frataxin and Mitochondrial Dysfunction in Friedreich's Ataxia

Giovanni Manfredi, MD, PhD, Professor of Neurology and Neuroscience, Weill Medical College of Cornell University

Role of Frataxin and Mitochondrial Dysfunction in Friedreich's Ataxia

Giovanni Manfredi, MD, PhD, Professor of Neurology and Neuroscience, Weill Medical College of Cornell University

Occurrence of adverse events in chronic intrathecal baclofen infusion: a one-year follow-up study of 158 adults

Occurrence of adverse events in chronic intrathecal baclofen infusion: a one-year follow-up study of 158 adults. Léo Borrini, Djamel Bensmail, Jean-Baptiste Thiebaut, Caroline Hugeron, Célia Rech, Claire Jourdan; Archives of Physical Medicine and Rehabilitation, Available online 6 January 2014. http://dx.doi.org/10.1016/j.apmr.2013.12.019

The objective is to assess the frequency and types of adverse events (AEs) related to intrathecal baclofen (ITB) therapy in adults, and associated risk factors.

Keywords: Baclofen, Implantable pump, Spasticity, Adverse event

MITOCHONDRIA: Mitochondrial OXPHOS (dys) function ex-vivo - the use of primary fibroblasts

MITOCHONDRIA: Mitochondrial OXPHOS (dys) function ex-vivo - the use of primary fibroblasts. Ann Saada, The International Journal of Biochemistry & Cell Biology, Available online 7 January 2014. http://dx.doi.org/10.1016/j.biocel.2013.12.010

Is summarized in this review the usefulness of fibroblasts in culture to verify and study the pathomechanism of new mitochondrial diseases and to evaluate the efficacy of individual treatment options.
The rationale for screening vitamins is that they frequently function as substrates and co-enzymes or as antioxidants and electron donors.

The kinetics of folding of frataxin

The kinetics of folding of frataxin. Daniela Bonetti, Angelo Toto, Rajanish Giri, Angela Morrone, Domenico Sanfelice, Annalisa Pastore, PA Temussi, Stefano Gianni and M Brunori; hys. Chem. Chem. Phys., 2014, Accepted Manuscript DOI: 10.1039/C3CP54055C

HFE p.C282Y heterozygosity is associated with earlier disease onset in Friedreich ataxia

HFE p.C282Y heterozygosity is associated with earlier disease onset in Friedreich ataxia; Delatycki, M. B., Tai, G., Corben, L., Yiu, E. M., Evans-Galea, M. V., Stephenson, S. E.M., Gurrin, L., Allen, K. J., Lynch, D. and Lockhart, P. J.; Mov. Disord.. doi: 10.1002/mds.25795

Keywords: Friedreich ataxia; HFE; hemochromatosis; genetic modifier; disease severity

Molecular and clinical investigation of Iranian patients with friedreich ataxia.

Molecular and clinical investigation of Iranian patients with friedreich ataxia.. Salehi MH, Houshmand M, Aryani O, Kamalidehghan B, Khalili E., Iran Biomed J. 2014 Jan;18(1):28-33.

BIOMARKERS IN RARE NEUROMUSCULAR DISEASES

BIOMARKERS IN RARE NEUROMUSCULAR DISEASES . Chiara Scotton, Chiara Passarelli, Marcella Neri, Alessandra Ferlini; Experimental Cell Research, Available online 31 December 2013.

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Agilis Biotherapeutics and Intrexon to Pursue Transformative Therapies for Rare Genetic Disease

Agilis Biotherapeutics and Intrexon to Pursue Transformative Therapies for Rare Genetic Disease. NEW YORK and GERMANTOWN, Md., Dec. 31, 2013 /PRNewswire.

Agilis Biotherapeutics, LLC, a synthetic biology-based company focused on rare genetic diseases, and Intrexon Corporation (NYSE: XON), a leader in synthetic biology, announced today an Exclusive Channel Collaboration (ECC) to develop DNA-based therapeutics for Friedreich's ataxia (FRDA), a rare genetic neurodegenerative disease.