Triple Therapy with Darbepoetin Alfa, Idebenone, and Riboflavin in Friedreich’s Ataxia: an Open-Label Trial

Triple Therapy with Darbepoetin Alfa, Idebenone, and Riboflavin in Friedreich’s Ataxia: an Open-Label Trial. Javier Arpa, Irene Sanz-Gallego, Francisco J. Rodríguez-de-Rivera, Francisco J. Domínguez-Melcón, Daniel Prefasi, Javier Oliva-Navarro, Mar Moreno-Yangüela, Samuel I. Pascual-Pascual. The Cerebellum April 2013 DOI 10.1007/s12311-013-0482-y



Long-term statistically nonsignificant improvement of LVMI and stability of the echocardiographic parameters could be considered. Triple therapy may slow disease progression of FRDA.

Progress in gene therapy for neurological disorders

Progress in gene therapy for neurological disorders. Michele Simonato, Jean Bennett, Nicholas M. Boulis, Maria G. Castro, David J. Fink, William F. Goins, Steven J. Gray, Pedro R. Lowenstein, Luk H. Vandenberghe, Thomas J. Wilson, John H. Wolfe & Joseph C. Glorioso; Nature Reviews Neurology , | doi:10.1038/nrneurol.2013.56

Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system.

Erythropoietin receptor (EpoR) agonism to treat a wide range of diseases.

Erythropoietin receptor (EpoR) agonism to treat a wide range of diseases. Sanchis-Gomar F, Perez-Quilis C, Lippi G.; Mol Med. 2013 Apr 11. doi: 10.2119/molmed.2013.00025.

Keywords: Erythropoietin receptor (EpoR), pleitropic actions, heart and cardiovascular diseases, neurodegenerative disorders (Parkinson and Alzheimer), spinal cord injury, stroke, diabetic retinopathy, rare diseases (Friedreich ataxia) side effects, non-hematopoietic EpoR agonists drugs (asialoEpo, Cepo and ARA 290)

Hereditary Ataxia and Spastic Paraplegia in Portugal: A Population-Based Prevalence Study.

Hereditary Ataxia and Spastic Paraplegia in Portugal: A Population-Based Prevalence Study. Coutinho P, Ruano L, Loureiro JL, Cruz VT, Barros J, Tuna A, Barbot C, Guimarães J, Alonso I, Silveira I, Sequeiros J, Marques Neves J, Serrano P, Silva MC
JAMA Neurology [2013:1-10]

Friedreich ataxia (prevalence, 1.0 per 100 000 population)

Scientists Find Way to Turn Stem Cells Into Brain Cells

Scientists Find Way to Turn Stem Cells Into Brain Cells. Jason Koebler, U.S. News & World. April 23, 2013.

New scholarship research into Friedreich Ataxia, heart and eye dysfunction

CERA student receives prestigious Gustav Nossal Scholarship for his research into Friedreich Ataxia .
CERA (Centre for Eye Research Australia).09 April, 2013

Duncan is a PhD student in CERA's Neuroregeneration Research Unit, he uses stem cells generated in the laboratory from FRDA patients' own skin, to grow certain types of cells found in the heart and eye. These cells will be used to better understand the pathology of FRDA, to conduct basic research on the disease and to test new drugs, prior to conducting clinical trials.

Gene Therapy for Rare Diseases: Summary of a National Institutes of Health Workshop, September 13, 2012

Gene Therapy for Rare Diseases: Summary of a National Institutes of Health Workshop, September 13, 2012 . Marina O'Reilly, Donald B. Kohn, Jeffrey Bartlett, Janet Benson, Philip J. Brooks, Barry J. Byrne, Carlos Camozzi, Kenneth Cornetta, Ronald G. Crystal, Yuman Fong, Linda Gargiulo, Rashmi Gopal-Srivastava, Katherine A. High, Samuel G. Jacobson, Robert C. Jambou, Maureen Montgomery, Eugene Rosenthal, R. Jude Samulski, Sonia I. Skarlatos, Brian Sorrentino, James M. Wilson, Yun Xie, and Jacqueline Corrigan-Curay. Human Gene Therapy. April 2013, 24(4): 355-362. doi:10.1089/hum.2013.064.

Gene therapy has shown clinical efficacy for several rare diseases, using different approaches and vectors.

Of flies and men: insights on organismal metabolism from fruit flies

Of flies and men: insights on organismal metabolism from fruit flies. Akhila Rajan and Norbert Perrimon; BMC Biology 2013, 11:38 doi:10.1186/1741-7007-11-38

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Altered lipid metabolism in human neurodegenerative disease models

Given the energy needs of neuronal cells, it is not surprising that deficits in energy metabolism manifest themselves most prominently in neuronal cell types. Genes that play a role in lipid homeostasis and mitochondrial function have been linked to adult onset neurodegeneration and have been extensively reviewed elsewhere [4,51,52]. Here we discuss insights obtained from a fly model of Friedreich's ataxia (FRDA) [53]. FRDA is the most common form of an autosomal recessive neurodegenerative disease affecting the central and peripheral nervous systems. It is caused by reduced expression of the mitochondrial protein frataxin, whose deficiency affects citric acid cycle function. Diabetes is a typical symptom of FRDA patients, and electron microscopic analysis of the neurons and cardiac muscles in mouse models shows an increase in lipid droplets [54], suggesting that there may be changes in lipid metabolism. To pursue further the role played by abnormal lipid metabolism in FRDA pathogenesis, Drosophila frataxin was removed from glial cells (neuronal support cells) by RNA interference (RNAi). This resulted in increased lipid droplet accumulation in glial cells and increased sensitivity to oxidative insults, neurodegeneration and impairment in locomotor activity. Interestingly, overexpression of Glial Lazarillo (GLaz) - the Drosophila homolog of human apolipoprotein D, a carrier protein of lipids - confers a protective effect on the Frataxin-RNAi flies. These studies suggest for the first time a specific requirement for frataxin in glial cells, and open the possibility that the control of lipid metabolism by apolipoproteins could represent a new strategy for the treatment of FRDA patients.

Lysine deacetylases and mitochondrial dynamics in neurodegeneration.

Lysine deacetylases and mitochondrial dynamics in neurodegeneration. Pedro Guedes-Dias, Jorge M.A. Oliveira; Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Available online 8 April 2013

Keywords: Mitochondria, HDAC, sirtuins, mitochondrial dynamics, biogenesis, mitophagy.

The L-Cysteine Desulfurase NFS1 Is Localized in the Cytosol where it Provides the Sulfur for Molybdenum Cofactor Biosynthesis in Humans

The L-Cysteine Desulfurase NFS1 Is Localized in the Cytosol where it Provides the Sulfur for Molybdenum Cofactor Biosynthesis in Humans,Zvonimir Marelja, Mita Mullick Chowdhury, Carsten Dosche, Carsten Hille, Otto Baumann, Hans-Gerd Löhmannsröben, Silke Leimkühler; PLoS ONE 8(4): e60869. doi:10.1371/journal.pone.0060869

Fifth Congress of the International BioIron Society (IBIS) (BioIron 2013) at University College London.

Fifth Congress of the International BioIron Society (IBIS) (BioIron 2013) at
University College London. 2013 Program Book - International BioIron Society, April 14-18

Podium #36
IRP-1 CONTROLS IRON METABOLISM IN FRATAXIN-DEFICIENT TISSUES
Alain Martelli, PhD, Stéphane Schmucker, PhD, Laurence Reutenauer, Hervé Puy, Prof., Bruno Galy, PhD, Matthias
Hentze, Prof. and Hélène Puccio, Research Director

Podium #47
ABNORMAL BODY IRON DISTRIBUTION AND ERYTHROPOIESIS IN A NOVEL MOUSE MODEL WITH INDUCIBLE GAIN
OF IRON REGULATORY PROTEIN (IRP) -1 FUNCTION
Daniela Casarrubea, MSc, Lydie Viatte, PhD, Tina Hallas, Aparna Vasanthakumar, PhD, Richard S. Eisenstein, PhD, Klaus
Schümann, PhD, Matthias W. Hentze, PhD and Bruno Galy, PhD

Podium #66
IDENTIFICATION OF NONFERRITIN MITOCHONDRIAL IRON DEPOSITS IN A MOUSE MODEL OF FRIEDREICH ATAXIA
Des R. Richardson, M. Whitnall, Y. Suryo Rahmant, M.L.H. Huang, F. Saletta, H.C. Lok, L. Gutierrez, F.J. Lazaro, A.J.
Fleming, T.G. St Pierre, M.R. Mikhael and P. Ponka

Poster #34
MITOCHONDRIAL PROTEIN, FRATAXIN, IS DOWNREGULATED IN HEMODIALYSIS PATIENTS
Takeshi Nakanishi, MD, PhD; Yukiko Hasuike, MD,PhD; Soshi Yorifuji, MD; Ayako Matsumoto, MD; Mana Yahiro, MD, PhD;
Aritoshi Kida, MD; Yasuyuki Nagasawa, MD, PhD; Takahiro Kuragano, MD, PhD

Poster #35
FRATAXIN IS A REGULATOR OF THE FE-S BIOGENESIS
Salvatore Adinolfi, biologist

Poster #39
MITOCHONDRIA-TARGETED IRON CHELATORS FOR THE MONITORING AND ADJUSTMENT OF CELLULAR LABILE
IRON POOLS
Vincenzo Abbate, PhD; Robert Hider, PhD; Charareh Pourzand, PhD; Olivier Reelfs, PhD

Poster #62
DOWN REGULATION OF RESPIRATORY ENZYMES IN FRATAXIN DEFICIENT YEAST IS MEDIATED BY THE
METABOLIC REGULATORS ADR1 AND CTH2
David Alsina, Armando Moreno-Cermeño, Elia Obis, Joaquim Ros and Jordi Tamarit

Poster #64
DEFINING THE ARCHITECTURE OF THE MITOCHODRIAL IRON-SULFUR CLUSTER ASSEMBLY MACHINERY
Belinda Galean

Poster #214
A CELL MODEL FOR FRIEDREICH ATAXIA USING DORSAL ROOT GANGLIA NEURONS
Stefka Mincheva-Tasheva, PhD, Elia Obis, Joaquim Ros, PhD and Jordi Tamarit, PhD

Poster #231
NOVEL LIGHT-ACTIVATED CAGED IRON CHELATORS: TARGETED PRODRUGS FOR IRON RELATED-DISORDERS
Benjamin Young, MPharm, Olivier Reelfs, PhD, DSc, Asma Aroun, PhD, Seyed Ali Miri, BSc, Magnus Hoffmann, BSc,
Charareh Pourzand, PhD, DSc and Ian Eggleston

Poster #273
A PRIMARY CULTURE OF CARDIOMYOCYTES WITH FRATAXIN DEFICIENCY EXHIBITS A METABOLIC SWITCH
BEFORE IRON DISARRANGEMENTS
Elia Obis, David Alsina, Joaquim Ros and Jordi Tamarit

Therapeutic Strategies in Friedreich's Ataxia

Therapeutic Strategies in Friedreich's Ataxia. Timothy E. Richardson, Heather N. Kelly, Amanda E. Yu, James W. Simpkins; Brain Research, Available online 13 April 2013. http://dx.doi.org/10.1016/j.brainres.2013.04.005

Keywords: Friedreich's ataxia (FA), FXN, frataxin, therapeutic research, ongoing treatment strategies, 17β-estradiol, methylene blue.

Cardiomyopathy and the electrocardiogram in Friedreich's ataxia

Cardiomyopathy and the electrocardiogram in Friedreich's ataxia . Alexandra H Wood, Simon W Dubrey; British Journal of Hospital Medicine, Vol. 74, Iss. 4, 09 Apr 2013, pp 232 - 233

Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden

Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden. Ilaria Pelizzoni, Daniele Zacchetti, Alessandro Campanella, Fabio Grohovaz, Franca Codazzi; Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Available online 11 April 2013. http://dx.doi.org/10.1016/j.bbadis.2013.04.007

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Keywords: Astrocytes, NTBI, iron uptake, DMT1, activation process, TRP channels, neuroinflammation

Vitamin Switches on a Gene, A Potential New Treatment for Friedreich's Ataxia?

Vitamin Switches on a Gene, A Potential New Treatment for Friedreich's Ataxia?. MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London.

Novel research from the CSC holds promise for a new therapeutic approach, using a commonly available vitamin supplement to modify the epigenetic controls of the genetic defect causing the illness.

Related to: Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by Vitamin B3

Frataxin Deficiency Leads to Reduced Expression and Impaired Translocation of NF-E2-Related Factor (Nrf2) in Cultured Motor Neurons

Frataxin Deficiency Leads to Reduced Expression and Impaired Translocation of NF-E2-Related Factor (Nrf2) in Cultured Motor Neurons. D'Oria, V.; Petrini, S.; Travaglini, L.; Priori, C.; Piermarini, E.; Petrillo, S.; Carletti, B.; Bertini, E.; Piemonte, F.; International Journal of Molecular Sciences. 2013; 14(4):7853-7865.

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Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases

Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases. Rajnish K. Chaturvedi, M. Flint Beal. Molecular and Cellular Neuroscience, Volume 55, July 2013, Pages 101-114. http://dx.doi.org/10.1016/j.mcn.2012.11.011

Keywords: Parkinson's disease, Huntington's disease, Neurodegenerative diseases, Mitochondrial dysfunction, Creatine, Co-Q10, PGC-1α, Sirtuins.

Cerebello-cerebral connectivity deficits in Friedreich ataxia

Cerebello-cerebral connectivity deficits in Friedreich ataxia. Andrew Zalesky, Hamed Akhlaghi, Louise A. Corben, John L. Bradshaw, Martin B. Delatycki, Elsdon Storey, Nellie Georgiou-Karistianis, Gary F. Egan. Brain Structure and Function, April 2013. DOI 10.1007/s00429-013-0547-1

Keywords: Friedreich ataxia, Diffusion-weighted imaging, White matter, Connectome, Connectivity, supplementary motor area, cingulate cortex, frontal cortices, putamen, other subcortical nuclei.

Mitochondrial Diseases of the Brain

Mitochondrial Diseases of the Brain. Rajnish K. Chaturvedi, M. Flint Beal; Free Radical Biology and Medicine, Available online 6 April 2013.
http://dx.doi.org/10.1016/j.freeradbiomed.2013.03.018

Keywords: Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Friedreich’s ataxia, Neurodegenerative diseases, Mitochondrial dysfunction, Creatine, Co-Q10, PGC-1α, Sirtuins.

Moving Forward on Shifting Sands: Ethical Regulation of Gene Therapy Clinical Trials in the United Kingdom

Moving Forward on Shifting Sands: Ethical Regulation of Gene Therapy Clinical Trials in the United Kingdom. Emma Morris, Martin Gore, Andrew Baker and Adrian J Thrasher; Molecular Therapy (2013); 21 4, 715–716. doi:10.1038/mt.2013.43

Editorial. FULL TEXT

Gene Therapy Researchers' Assessments Of Risks And Perceptions Of Risk Acceptability In Clinical Trials

Gene Therapy Researchers' Assessments Of Risks And Perceptions Of Risk Acceptability In Clinical Trials. Claire T. Deakin, Ian E. Alexander, Cliff A. Hooker, Ian H. Kerridge; Molecular Therapy (2013); 21 4, 806–815. doi:10.1038/mt.2012.230

Decisions about clinical trials appear to be influenced not only by the clinical context and preclinical evidence. Identifying moral assumptions and qualitative assessments underpinning the design and conduct of research may facilitate future decision-making in clinical trials.

The effect of nicotinamide on dysregulated genes associated with frataxin deficiency in FRDA.

The effect of nicotinamide on dysregulated genes associated with frataxin deficiency in FRDA. Chan PK, Khadayate S; Gene Expression Omnibus (GEO). Public on Apr 03, 2013

Citation: Chan PK, Torres R, Yandim C, Law PP et al. Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum Mol Genet 2013 Mar 26. PMID: 2347481

Genetic and phenotypic variability of optic neuropathies.

Genetic and phenotypic variability of optic neuropathies. Neuhann T, Rautenstrauss B.; Expert Rev Neurother. 2013 Apr;13(4):357-67. doi: 10.1586/ern.13.19.

Keywords: Hereditary optic neuropathies, heterogeneous disorders, autosomal dominant, autosomal recessive, X-linked recessive, Leber's hereditary optic neuropathy, Kjer's disease, mtDNA mutations, inherited peripheral neuropathies, Charcot-Marie-Tooth disorders (CMT2A2, CMTX5), hereditary sensory neuropathy type 3 (HSAN3), Friedreich's ataxia, leukodystrophies, sphingolipidoses, ceroid-lipofuscinoses, brain iron accumulation.

Cis-silencing of PIP5K1B evidenced in Friedreich's ataxia patient cells results in cytoskeleton anomalies

Cis-silencing of PIP5K1B evidenced in Friedreich's ataxia patient cells results in cytoskeleton anomalies . Aurélien Bayot, Sacha Reichman, Sophie Lebon, Zsolt Csaba, Laetitia Aubry, Ghislaine Sterkers, Isabelle Husson, Malgorzata Rak, Pierre Rustin; Hum. Mol. Genet. (2013) doi: 10.1093/hmg/ddt144 First published online: April 2, 2013.

KEYWORDS: Friedreich's ataxia (FRDA), intronic expansion of GAA triplet repeats, FXN locus, mitochondrial frataxin, profound cytoskeleton anomalies, PIP5K1B gene, phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), phosphatidylinositol 4-phosphate (PI(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), actin network.

The role of palliative care in patients with neurological diseases

The role of palliative care in patients with neurological diseases. Gian Domenico Borasio; Nature Reviews Neurology ,doi:10.1038/nrneurol.2013.49

Keywords:Palliative care, quality of life, life-threatening illness, neurological disorders, daily clinical practice.

Trinucleotide repeat expansions catalyzed by human cell-free extracts

Trinucleotide repeat expansions catalyzed by human cell-free extracts. Jennifer R Stevens, Elaine E Lahue, Guo-Min Li and Robert S Lahue. Cell Research (2013) 23:565–572. doi:10.1038/cr.2013.12; published online 22 January 2013

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A phase IIa clinical trial to test the safety and efficacy of interferon gamma treatment in elevating frataxin levels in Friedreich’s ataxia (FRDA) patients.

A phase IIa clinical trial to test the safety and efficacy of interferon gamma treatment in elevating frataxin levels in Friedreich’s ataxia (FRDA) patients. Dr Roberto Testi, Universita’ di Roma Tor Vergata, Italy.

New research project