Therapies in inborn errors of oxidative metabolism

Therapies in inborn errors of oxidative metabolism. Manuel Schiff, Paule Bénit, Howard T. Jacobs, Jerry Vockley and Pierre Rustin. Trends in Endocrinology & Metabolism, 29 May 2012, doi:10.1016/j.tem.2012.04.006.

Keywords: Mitochondrial diseases, mitochondrial dysfunction, 2000 genes, epigenetic and environmental factors, decreased ATP, targets and mechanism of action.

"The manifestations of mitochondrial dysfunction and the response to therapy vary between individuals". This statement by the authors of the paper shows perfectly the great difficulty of the FA's therapeutic approach, and may explain why do not exist two patients who progress in the same way, even siblings.

Molecular genetic diagnostics of Friedreich's ataxia. Ten years' experience based on analysis of blood samples.

Molecular genetic diagnostics of Friedreich's ataxia. Ten years' experience based on analysis of blood samples.[Article in Hungarian] Kisfali P, Melegh B. Orv Hetil. 2012 Jun 1;153(22):852-5.

Keywords:  frataxin,  molecular genetic diagnosis, Friedreich's ataxia, blood samples.

An Open Label Clinical Pilot Study of Resveratrol as a Treatment for Friedreich Ataxia

An Open Label Clinical Pilot Study of Resveratrol as a Treatment for Friedreich Ataxia 13th Asian Oceanian Congress of Neurology, 4–8 June 2012, Melbourne Convention and Exhibition Centre, Melbourne, Australia
Keywords: Friedreich ataxia (FRDA), mitochondrial protein frataxin, Resveratrol, anti-oxidant, neuroprotective, open-label sequential clinical pilot study, lymphocyte frataxin levels.

Neuron Function Restored in Brains Damaged by Huntington's Disease

Neuron Function Restored in Brains Damaged by Huntington's Disease Van Andel Research Institute (2012, May 29). Neuron function restored in brains damaged by Huntington's disease. ScienceDaily. Retrieved

ScienceDaily (May 29, 2012) — Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models.

It is always good to look the advances in neurodegenerative diseases more frequents than FA, a long way is needed to became a human therapy, but neuroscience and cell biology are progressing rapidly

Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia.

Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia. Int J Cardiol. 2012 May 25. [Epub ahead of print]. Friedman LS, Schadt KA, Regner SR, Mark GE, Lin KY, Sciascia T, St John Sutton M, Willi S, Lynch DR.

Keywords: Friedreich ataxia, ataxia, dysarthria, areflexia, cardiomyopathy, cardiac troponin I, acute myocardial infarction, echocardiogram parameters, ejection fraction, electrocardiograms.

Neurological disorders in the 11th revision of the International Classification of Diseases: now open to public feedback

Neurological disorders in the 11th revision of the International Classification of Diseases: now open to public feedback. The Lancet Neurology, Farrah J Mateen, Tarun Dua, Gordon C Shen, Geoffrey M Reed, Raad Shakir, Shekhar Saxena. Volume 11, Issue 6, Pages 484 - 485, June 2012, doi:10.1016/S1474-4422(12)70125-4

Keywords: WHO International Classification of Diseases (ICD), taxonomy, international standard, 11th revision,

The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.

The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism. Lill R, Hoffmann B, Molik S, Pierik AJ, Rietzschel N, Stehling O, Uzarska MA, Webert H, Wilbrecht C, Mühlenhoff U.Biochim Biophys Acta. 2012 May 15.

 Keywords: Mitochondria, iron metabolism, synthesize heme, assemble iron-sulfur (Fe/S) proteins, cellular iron regulation, mitochondrial Fe/S cluster (ISC), cysteine desulfurase complex Nfs1-Isd11, ferredoxin-ferredoxin reductase, frataxin, scaffold protein Isu1, Hsp70 chaperone, glutaredoxin Grx5.

This article is part of a Special Issue entitled: Cell Biology of Metals.

TR3-05471: iPSC-derived Friedreich's ataxia

TR3-05471: iPSC-derived Friedreich's ataxia. CIRN, California Institute for Regenerative Medecine.
Recommendation: Not Recommended for Funding Scientific Score: --Total Funds Requested $6,521,212 Award Type : Development Candidate Award.

Not all are good news

Ultrasound-guided nerve blocks in the Charcot–Marie–Tooth disease and Friedreich's ataxia

Ultrasound-guided nerve blocks in the Charcot–Marie–Tooth disease and Friedreich's ataxia. J. B. Barbary, F. Remérand, J. Brilhault, M. Laffon J. Fusciardi. Br. J. Anaesth. (2012) 108 (6): 1042-1043. doi: 10.1093/bja/aes160

Keywords: Peripheral nerve blocks (PNBs), neurological disease, electrical stimulation, ultrasound-guided PNBs, neurofibromatosis, hypertrophic peripheral neuropathy [Charcot–Marie–Tooth disease type 1 (CMTD1)], Friedreich's ataxia (FRA).

Resveratrol Protects Cortical Neurons against Microglia-mediated Neuroinflammation

Resveratrol Protects Cortical Neurons against Microglia-mediated Neuroinflammation, Zhang, F., Wang, H., Wu, Q., Lu, Y., Nie, J., Xie, X. and Shi, J. (2012), Phytother. Res.. doi: 10.1002/ptr.4734

 Keywords: resveratrol, neuroprotection, neuroinflammation, microglial activation, neurological disorders.

  I would like to stress that currently in Australia is running a clinical trial in FA patients, we are looking forward to its findings

TALE proteins induced the expression of the frataxin gene.

TALE proteins induced the expression of the frataxin gene. Prof. Jacques P Tremblay, Mr. Pierre Chapdelaine, Zoé Coulombe, and Joël Rousseau. Human Gene Therapy. -Not available-, ahead of print. doi:10.1089/hum.2012.034.

 The TALEFrat increased by 2 to 3 folds the frataxin gene expression and potentially could alleviate the symptoms of Friedreich ataxia.

Keywords: Tal effector proteins(TALE), transcription activator, expression of a gene, Friedreich ataxia (FRDA), frataxin, TALE genes (TALEFrat), VP16 peptides, mCherry reporter gene

Worldwide status of clinical experimentation with stem cells in neurologic diseases

Worldwide status of clinical experimentation with stem cells in neurologic diseases. Dimitrios Karussis, MD, PhD. Neurology April 24, 2012 78:1334-1336.

KEYWORDS: stem cells, CNS repair, Embryonic stem cells (ESC), pluripotent, potential carcinomatous transformation, somatic stem cells, neuronal (NSC), mesenchymal stem cells (MSC), Fetal NSC, ethical, legislative, immunomodulatory effects, neurotrophic factors, bone marrow, blood–brain barrier, animal models of neurologic disorders.

Friedreich's Ataxia Causes Redistribution of Iron, Copper, and Zinc in the Dentate Nucleus.

Friedreich's Ataxia Causes Redistribution of Iron, Copper, and Zinc in the Dentate Nucleus. Koeppen AH, Ramirez RL, Yu D, Collins SE, Qian J, Parsons PJ, Yang KX, Chen Z, Mazurkiewicz JE, Feustel PJ.. Cerebellum. 2012 May 5. [Epub ahead of print].

 Keywords:Friedreich's ataxia (FRDA), large neurons, dentate nucleus (DN), iron (Fe), copper (Cu), zinc (Zn), quantitative X-ray fluorescence (XRF), hilar white matter, DN gray matter, oligodendroglia.

Spinal Cord Atrophy Correlates with Disability in Friedreich's Ataxia.

Spinal Cord Atrophy Correlates with Disability in Friedreich's Ataxia. Chevis CF, da Silva CB, D'Abreu A, Lopes-Cendes I, Cendes F, Bergo FP, França MC. Cerebellum 2012 May 5.

Keywords: Friedreich's ataxia, spinal cord atrophy, spinal cord area, eccentricity at C2/C3 level, Friedreich ataxia rating scale (FARS).

What the Orphan Drug Act Has Done Lately for Children With Rare Diseases: A 10-Year Analysis

What the Orphan Drug Act Has Done Lately for Children With Rare Diseases: A 10-Year Analysis. Chandana Thorat, BTech, Kui Xu, MD, PhD, Scott N. Freeman, PhD, Renan A. Bonnel, PharmD, MPH, Francesca Joseph, MD, M. Ian Phillips, PhD, DSc, Menfo A. Imoisili, MD, MPH. Pediatrics Vol. 129 No. 3 March 1, 2012. pp. 516 -521 (doi: 10.1542/peds.2011-1798)

KEYWORDS: orphan drugs, rare diseases, Orphan Drug Act, pediatrics

Induced neural stem cells: a new tool for studying neural development and neurological disorders

Induced neural stem cells: a new tool for studying neural development and neurological disorders. Cell Research advance online publication 1 May 2012; doi: 10.1038/cr.2012.73, Guang-Hui Liu, Fei Yi, Keiichiro Suzuki, Jing Qu, Juan Carlos Izpisua Belmonte.
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing China. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Center for Regenerative Medicine in Barcelona, 08003 Barcelona, Spain.

Recent advances in the generation of multipotent and expandable induced neural stem cells are exciting. They not only hold great promises for potential clinical applications but may also open up a new era for neural stem cell research in the near future.

alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorganic & Medicinal Chemistry Letters 21 (2011) 3693–3698, William D. Shrader, Akiko Amagata, Adam Barnes, Gregory M. Enns, Andrew Hinman, Orion Jankowski , Viktoria Kheifets, Ryo Komatsuzaki, Edgar Lee, Paul Mollard, Katsuyuki Murase, Alfredo A. Sadun, Martin Thoolen, Kieron Wesson, Guy Miller.

Keywords: Redox, Antioxidants, Quinone, Aging, Digital Biology, frataxin, Friedreich's Ataxia.

The role of hydration in protein stability: comparison of the cold and heat unfolded states of Yfh1.

The role of hydration in protein stability: comparison of the cold and heat unfolded states of Yfh1. JMol Biol. 2012Apr 13;417(5):413-24. Epub 2012 Feb 14. Adrover M, Martorell G, Martin SR, Urosev D, Konarev PV, Svergun DI, Daura X, Temussi P, Pastore A.

Keywors: Protein unfolding, high- and low-temperature unfolded states, Yfh1, residual secondary structures, protein stability.

The State of Gene Therapies: The FDA Perspective

The State of Gene Therapies: The FDA Perspective, Molecular Therapy (2012); 20 5, 877–878. doi:10.1038/mt.2012.51, Daniel Takefman and Wilson Bryan Full Text.

Keywords: Clinical development of gene therapy, 320 ongoing gene therapy clinical trials, Office of Cellular Tissue and Gene Therapies (OCTGT), Center for Biologics Evaluation and Research of the US Food and Drug Administration (FDA), treatments for specific, well-defined genetic disorders ... Full Text.

Human adipose stem cell-conditioned medium increases survival of Friedreich’s ataxia cells submitted to oxidative stress

Human adipose stem cell-conditioned medium increases survival of Friedreich’s ataxia cells submitted to oxidative stress . Dr. Jonathan Jones, Mrs. Alicia Estirado, Dr. Carolina Redondo, Dr. Carlos Bueno, and Salvador Martinez. Stem Cells and Development. doi:10.1089/scd.2012.0029.

Keywords: Friedreich’s ataxia, progressive gait, ataxia, cardiomyopathy, in vitro, adult stem cells, periodontal ligament cells, oxidative stress, adipose stem cell-conditioned medium, trophic factors, BDNF (brain-derived neurotrophic factor.

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.Brain Cogn. 2012 Apr 27;79(3):200-208. [Epub ahead of print], Georgiou-Karistianis N, Akhlaghi H, Corben LA, Delatycki MB, Storey E, Bradshaw JL, Egan GF.

Keyword: Simon effect task, functional brain reorganization, Friedreich ataxia (FRDA), magnetic resonance imaging (fMRI).

Accelerating progress in iPS cell research for neurological diseases

Accelerating progress in iPS cell research for neurological diseases. Daisuke Ito, Hideyuki Okano and Norihiro Suzuki, Annals of Neurology, Accepted manuscript online: 29 MAR 2012 06:18AM EST | DOI: 10.1002/ana.23596 Keywords: induced pluripotent stem cells (iPSCs), pluripotency, embryonic stem cells (ESCs, personalized replacement therapy, elucidate the pathological processes, neurodegenerative diseases, drug discovery, regenerative medicine.