Current Concepts and Controversies in Neurodegeneration with Brain Iron Accumulation

Current Concepts and Controversies in Neurodegeneration with Brain Iron Accumulation. Michael J. Keogh, BMBS, MSc, MRCP, Patrick F. Chinnery, MBBS, PhD, FRCP, FMedSc. Seminars in Pediatric Neurology Volume 19, Issue 2, June 2012, Pages 51–56. DOI: http://dx.doi.org/10.1016/j.spen.2012.03.004

Keywords: Neurodegeneration, brain iron accumulation (NBIA), phenotypic heterogeneity, NBIA pathogenesis.

The Case for Induced Pluripotent Stem Cell-derived Cardiomyocytes in Pharmacological Screening

The Case for Induced Pluripotent Stem Cell-derived Cardiomyocytes in Pharmacological Screening.Jaffar M Khan, Alexander R. Lyon and Sian E. Harding; British Journal of Pharmacology. Accepted manuscript online: 27 JUL 2012 DOI: 10.1111/j.1476-5381.2012.02118.x

Keywords: cardiac, stem cell, embryonic, iPSC, safety, cardiotoxicity, high throughput, drug screening models, human cardiomyocytes, pharmacology.

The Spectrum of Left Ventricular Changes in Friedreich Ataxia—Relation to Age and GAA Repeats in the Frataxin Gene

The Spectrum of Left Ventricular Changes in Friedreich Ataxia—Relation to Age and GAA Repeats in the Frataxin Gene. G. Romanelli, M. Delatycki, L. Donelan, R. Hassam, L. Corben, R. Peverill. Heart, Lung and Circulation, Volume 21, Supplement 1, 2012, Pages S273 DOI: http://dx.doi.org/10.1016/j.hlc.2012.05.668

Keywords: Increased LV RWT, GAA1, LV size, wall thickness or mass, age.

Echocardiographic Parameters in the Assessment of Friedreich's Ataxia with Preserved Left Ventricular Systolic Function

Echocardiographic Parameters in the Assessment of Friedreich's Ataxia with Preserved Left Ventricular Systolic Function. L. Eng, D. Duncan, I. Cukovski, L. Jijnasu, K. Davies, P. Palka. Heart, Lung and Circulation Volume 21, Supplement 1, 2012, Pages S201–S202. http://dx.doi.org/10.1016/j.hlc.2012.05.499.

Keyword: Friedreich's ataxia (FRDA), cardiac dysfunction, ,FRDA cardiomyopathy, left ventricular hypertrophy, diastolic dysfunction, myocardial dysfunction, echocardiographic, cardiac dimensions, Doppler imaging (TDI).

Epigenetic mechanisms governing the process of neurodegeneration

Epigenetic mechanisms governing the process of neurodegeneration. Irfan A. Qureshi, Mark F. Mehler. Molecular Aspects of Medicine, Available online 7 July 2012. DOI: http://dx.doi.org/10.1016/j.mam.2012.06.011

 Keywords: Chromatin, Epigenetic, Histone deacetylase, Histone modification, Neurodegenerative disease, Non-coding RNA.

Unanswered Questions in Friedreich Ataxia.

Unanswered Questions in Friedreich Ataxia. Lynch DR, Deutsch EC, Wilson RB, Tennekoon G.J Child Neurol. 2012 Jul 25. [Epub ahead of print]

Diabetes Mellitus in Children and Adolescents with Genetic Syndromes.

Diabetes Mellitus in Children and Adolescents with Genetic Syndromes.Schmidt F, Kapellen TM, Wiegand S, Herbst A, Wolf J, Fröhlich-Reiterer EE, Rabl W, Rohrer T, Holl RW; for the DPV-Wiss Study Group and the BMBF Competence Network Diabetes.Exp Clin Endocrinol Diabetes. 2012 Mar 22.

 Keywords: genetic syndromes, diabetes mellitus (DM), DPV database, frequency, treatment strategies, long-term complications, paediatric DM patients, Turner syndrome (TS), Prader-Willi syndrome (PWS), Friedreich ataxia (FA), Alström syndrome (AS), Klinefelter syndrome (KS), Bardet-Biedl syndrome (BBS), Berardinelli-Seip syndrome (BSS), Down syndrome (DS).

Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection. Pablo M. Arce, Ruth Goldschmidt, Omar M. Khdour, Manikandadas M. Madathil, Jennifer Jaruvangsanti, Sriloy Dey, David M. Fash, Jeffrey S. Armstrong, Sidney M. Hecht. Bioorganic & Medicinal Chemistry, Available online 14 July 2012. DOI: http://dx.doi.org/10.1016/j.bmc.2012.07.005

Keywords: pyridinol analogues, neuroprotective, idebenone, antioxidants, mitochondrial function, electron transport chain, Reactive oxygen species.

A New And Powerful Class Of Antioxidants Could One Day Be A Potent Treatment For Parkinson's Disease

Georgia Health Sciences University. "A New And Powerful Class Of Antioxidants Could One Day Be A Potent Treatment For Parkinson's Disease." Medical News Today. MediLexicon, Intl., 25 Jul. 2012. Web.

 Acting on the target NRF2 could be also very interesting in the FA

Human Mesenchymal Stem Cells Increase Anti-oxidant Defences in Cells Derived from Patients with Friedreich's Ataxia.

Human Mesenchymal Stem Cells Increase Anti-oxidant Defences in Cells Derived from Patients with Friedreich's Ataxia. Dey R, Kemp K, Gray E, Rice C, Scolding N, Wilkins A.; Cerebellum. 2012 Jul 24

 Keywords: Friedreich's ataxia (FRDA), Oxidative damage, oxidative stress, frataxin deficiency, bone marrow-derived mesenchymal stem cells (MSCs), superoxide dismutase (1 and 2) enzymes, conditioned medium from human MSCs, nitric oxide-induced oxidative stress, PI(3) kinase/Akt.

Genetic testing in neurology

Genetic testing in neurology. Victoria Harrison, Andrea H. Nemeth; Medicine Volume 40, Issue 8, August 2012, Pages 463–467. DOI: http://dx.doi.org/10.1016/j.mpmed.2012.05.009

 Keywords: carrier testing, confidentiality, consent, diagnostic testing, genetic testing, neurogenetics, neurology, presymptomatic testing.

Ataxia

Ataxia. Georgina Burke, Simon Hammans. Medicine, Volume 40, Issue 8, August 2012, Pages 435–439. DOI: http://dx.doi.org/10.1016/j.mpmed.2012.05.004.

Keywords: ataxia, cerebellum, Creutzfeldt–Jakob disease, Friedreich's, multiple sclerosis, paraneoplastic, proprioception, spinocerebellar ataxia.

Role of resveratrol and its analogues in the treatment of neurodegenerative diseases: focus on recent discoveries.

Role of resveratrol and its analogues in the treatment of neurodegenerative diseases: focus on recent discoveries.V. Foti Cuzzola, R. Ciurleo, S. Giacoppo, S. Marino, P. Bramanti. CNS Neurol Disord Drug Targets. 2011 Nov;10(7):849-62. Keywords: Neurodegenerative diseases, inflammatory mechanism, blood-brain barrier, Resveratrol (RSV), cardio- and neuro-protection, immune regulation, cancer chemoprevention, tumor necrosis factor, cyclooxygenase 2, inducible nitric oxide synthase, interleukins.

European Medicines Agency gives first approval of gene therapy for rare disease

European Medicines Agency recommends first gene therapy for approval. European Medicines Agency, Press release 20/07/2012  

Gene therapy is a great hope for rare diseases of genetic origin, such as Friedreich's ataxia. This is a big step, gene therapy can come out the research laboratories and may be sold by a pharmaceutical laboratory, this authorization would boost the interest of pharmaceutical companies to invest in the development of these therapies.

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Gene, Stem Cell, and Future Therapies for Orphan Disease

State of the Art. Gene, Stem Cell, and Future Therapies for Orphan Disease. M Ian Phillips. Clinical Pharmacology & Therapeutics (2012); 92 2, 182–192. doi:10.1038/clpt.2012.82

FULL TEXT

The central role and mechanisms of β-cell dysfunction and death in Friedreich's ataxia-associated diabetes

The central role and mechanisms of β-cell dysfunction and death in Friedreich's ataxia-associated diabetes. Miriam Cnop, Mariana Igoillo-Esteve, Myriam Rai, Audrey Begu, Yasmina Serroukh, Chantal Depondt, Anyishai E Musuaya, Ihsane Marhfour, Laurence Ladrière, Xavier Moles Lopez, Dionysios Lefkaditis, Fabrice Moore, Jean-Pierre Brion, J Mark Cooper, Anthony HV Schapira, Anne Clark, Arnulf H Koeppen, Piero Marchetti, Massimo Pandolfo, Décio L Eizirik and Françoise Féry.  Annals of Neurology. Accepted manuscript online: 20 JUL 2012. DOI: 10.1002/ana.23698

Keywords: Friedreich's ataxia (FRDA), neurodegenerative disease, frataxin gene, diabetes, insulin resistance, β-cell failure, disposition index, Pancreatic β-cell dysfunction, mitochondrial dysfunction.

The Role of Academic Institutions in the Development of Drugs for Rare and Neglected Diseases

The Role of Academic Institutions in the Development of Drugs for Rare and Neglected Diseases. L D Coles and J C Cloyd. Clinical Pharmacology & Therapeutics (2012); 92 2, 193–202. doi:10.1038/clpt.2012.83.

The Future of Orphan Drug Development

The Future of Orphan Drug Development. J Woodcock. Clinical Pharmacology & Therapeutics (2012); 92 2, 146–148. doi:10.1038/clpt.2012.89

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Skeletal Muscle Involvement in Friedreich Ataxia and Potential Effects of Recombinant Human Erythropoietin Administration on Muscle Regeneration and Neovascularization

Skeletal Muscle Involvement in Friedreich Ataxia and Potential Effects of Recombinant Human Erythropoietin Administration on Muscle Regeneration and Neovascularization. Nachbauer W, Boesch S, Reindl M, Eigentler A, Hufler K, Poewe W, Löscher W, Wanschitz J.;J Neuropathol Exp Neurol. 2012 Jul 16.

Keywords: Friedreich ataxia (FRDA), frataxin, cardiac muscle involvement, mitochondrial dysfunction, skeletal muscle, recombinant human erythropoietin (rhuEPO), neurogenic and myopathic changes.

The Advocate is FARA's newsletter, Summer 2012

The Advocate is FARA's newsletter. It provides updates on FARA's activities including funded research, scientific conferences, and fundraising events

Summer 2012

Cell-Replacement Therapies For Neurological Conditions Via Neurons Derived From Cord Blood Cells

"Cell-Replacement Therapies For Neurological Conditions Via Neurons Derived From Cord Blood Cells." Medical News Today. MediLexicon, Intl., 18 Jul. 2012. Web.

Keywords: transcription factor, cord blood (CB) cells, neuron-like cells, neurological conditions, mesoderm, Sox2, future cell-replacement therapies.

Activating mitochondrial regulator PGC-1α expression by astrocytic NGF is a therapeutic strategy for Huntington's disease

Activating mitochondrial regulator PGC-1α expression by astrocytic NGF is a therapeutic strategy for Huntington's disease. Li-Wen Chen, Lin-Yea Horng, Chia-Ling Wu, Hui-Ching Sung, Rong-Tsun Wu. Neuropharmacology, Volume 63, Issue 4, September 2012, Pages 719-732. DOI: http://dx.doi.org/10.1016/j.neuropharm.2012.05.019

Keywords: Mitochondrial dysfunction, Huntington's disease (HD), NGF gene delivery, brain energy metabolism, neuroprotective effects, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), blood–brain barrier, astrocytic NGF inducer, Ganoderma lucidum (GaLu) extract.

Opportunities in systems biology to discover mechanisms and repurpose drugs for CNS diseases

Opportunities in systems biology to discover mechanisms and repurpose drugs for CNS diseases. Hongkang Mei, Tian Xia, Gang Feng, Jason Zhu, Simon Lin, Yang Qiu. Drug Discovery Today, Available online 29 June 2012. DOI: http://dx.doi.org/10.1016/j.drudis.2012.06.015

Keywords: Therapies, central nervous system (CNS) diseases, therapeutic targets, deciphering disease mechanisms, Multiple Level Network Modeling (MLNM) analysis.

The biomechanics of the reaching movement in Friedreich and stroke patients

The biomechanics of the reaching movement in Friedreich and stroke patients. M. Caimmi, M. Malosio, N. Pedrocchi, F. Vicentini, L. Molinari Tosatti, F. Molteni. Gait & Posture, Volume 36, Issue null, Page S88. DOI: http://dx.doi.org/10.1016/j.gaitpost.2011.10.331

Tat-Frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson’s disease

Tat-Frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson’s disease. Mi Jin Kim, Dae Won Kim, Hoon Jae Jeong, Eun Jeong Sohn, Min Jea Shin, Eun Hee Ahn, Soon Won Kwon, Young Nam Kim, Duk-Soo Kim, Jinseu Park, Won Sik Eum, Hyun Sook Hwang, Soo Young Choi. Biochimie, , Available online 14 July 2012. http://dx.doi.org/10.1016/j.biochi.2012.07.005

 Keywords: Frataxin, MPTP, Parkinson’s disease, Protein transduction domain, reactive oxygen species, dopaminergic neurons, blood brain barrier (BBB).

Role of mismatch repair enzymes in GAA-TTC triplet-repeat expansion in Friedreich's ataxia induced pluripotent stem cells (iPSCs)

Role of mismatch repair enzymes in GAA-TTC triplet-repeat expansion in Friedreich's ataxia induced pluripotent stem cells (iPSCs) . Jintang Du, Erica Campau, Elisabetta Soragni, Sherman Ku, James W. Puckett, Peter B. Dervan and Joel M. Gottesfeld. J. Biol. Chem. jbc.M112.391961. First Published on July 13, 2012, doi:10.1074/jbc.M112.391961

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Therapeutic Developments in Friedreich Ataxia

Therapeutic Developments in Friedreich Ataxia. Wilson RB, J Child Neurol 2012 Jul 12. doi: 10.1177/0883073812449691.

Keywords: Friedreich ataxia, neuro- and cardiodegenerative disorder, no approved therapy, frataxin, iron, oxidative stress, mitochondrial dysfunction.

DNA mismatch repair complex MutSbeta promotes GAA·TTC repeat expansion in human cells

DNA mismatch repair complex MutSbeta promotes GAA·TTC repeat expansion in human cells. Anasheh Halabi, Scott Ditch, Jeffrey Wang and Ed Grabczyk. The American Society for Biochemistry and Molecular Biology. Jbc, First Published on July 11, 2012, doi: 10.1074/jbc.M112.356758

Keywords: Friedreich Ataxia (FRDA), GAA·TTC repeat expansion, complex MutSbeta, MSH3 subunit, potential therapeutic target.

Gene therapy matures in the clinic

Gene therapy matures in the clinic. Leonard W Seymour & Adrian J Thrasher. Nature Biotechnology 30, 588–593 (2012) doi:10.1038/nbt.2290 Published online 10 July 2012.

Highlight: "will soon enter into mainstream medicine."

A functional MRI study of motor dysfunction in Friedreich's ataxia

A functional MRI study of motor dysfunction in Friedreich's ataxia. H. Akhalghi, L. Corben, N. Georgiou-Karistianis, J. Bradshaw, M.B. Delatycki, E. Storey, G.F. Egan. Brain Research, Available online 3 July 2012. http://dx.doi.org/10.1016/j.brainres.2012.06.035

Keywords: Friedreich's ataxia, Cerebellum, Finger tapping, proximal spinal cord, cortico-cerebellar, cortico-striatal, parieto-frontal.

Cardiomyopathy in Friedreich Ataxia: Clinical Findings and Research

Cardiomyopathy in Friedreich Ataxia: Clinical Findings and Research .Payne RM, Wagner GR. J Child Neurol 0883073812448535, July 4, 2012. doi: 10.1177/0883073812448535

Keywords: Friedreich ataxia, frataxin protein, iron-binding protein, mitochondrial matrix, mitochondrial oxidant stress, hypertrophic cardiomyopathy, heart failure.

Rationale for the Development of 2-Aminobenzamide Histone Deacetylase Inhibitors as Therapeutics for Friedreich Ataxia.

Rationale for the Development of 2-Aminobenzamide Histone Deacetylase Inhibitors as Therapeutics for Friedreich Ataxia. Soragni E, Xu C, Plasterer HL, Jacques V, Rusche JR, Gottesfeld JM. J Child Neurol. 2012 Jul 4. [Epub ahead of print]

Keywords: histone deacetylase inhibitors, neurodegenerative diseases, 2-aminobenzamides, frataxin (FXN) gene, Friedreich ataxia.

miR-886-3p Levels Are Elevated in Friedreich Ataxia

miR-886-3p Levels Are Elevated in Friedreich Ataxia. Lata H. Mahishi, Ronald P. Hart, David R. Lynch, and Rajiv R. Ratan. The Journal of Neuroscience, 4 July 2012, 32(27): 9369-9373; doi: 10.1523/​JNEUROSCI.0059-12.2012.

Keywords: Friedreich ataxia (FRDA), frataxin (FXN) gene, FXN RNA and protein levels, Small noncoding RNAs, hsa-miR-886-3p (miR-886-3p), novel therapeutic approach, anti-miR-886-3p.

The scale for the assessment and rating of ataxia correlates with dysarthria assessment in Friedreich's ataxia.

The scale for the assessment and rating of ataxia correlates with dysarthria assessment in Friedreich's ataxia. Eigentler A, Rhomberg J, Nachbauer W, Ritzer I, Poewe W, Boesch S.

Keywords: Dysarthria, neurogenic sensorimotor speech symptom, Frenchay Dysarthria Assessment, clinical and logopedic methodology, excellent clinical tool, ataxic speech disorders.

Clinical Monitoring in a Patient With Friedreich Ataxia and Osteogenic Sarcoma

Clinical Monitoring in a Patient With Friedreich Ataxia and Osteogenic Sarcoma . Deutsch EC, Seyer LA, Perlman SL, Yu J, Lynch DR. J Child Neurol 0883073812448460, first published on June 29, 2012 as doi:10.1177/0883073812448460

Keywords:  Friedreich ataxia, FXN, frataxin, lateral flow immunoassay, MAP chemotherapy.

Cross-Sectional Analysis of Electrocardiograms in a Large Heterogeneous Cohort of Friedreich Ataxia Subjects.

Cross-Sectional Analysis of Electrocardiograms in a Large Heterogeneous Cohort of Friedreich Ataxia Subjects.Schadt KA, Friedman LS, Regner SR, Mark GE, Lynch DR, Lin KY.J Child Neurol 0883073812448461, first published on June 29, 2012 as doi:10.1177/0883073812448461

Keywords:  Electrocardiographic (ECG) findings, Friedreich ataxia, ECG abnormalities, age, sex, shorter guanine-adenine-adenine triplet repeat length, age of disease onset, functional disability, nonspecific ST-T wave changes (53%), right axis deviation (32%), left ventricular hypertrophy (19%), right ventricular hypertrophy (13%).

Friedreich Ataxia: New Pathways.

Friedreich Ataxia: New Pathways.Pandolfo M., J Child Neurol 0883073812448534, first published on June 29, 2012 as doi:10.1177/0883073812448534

Keywords:  Friedreich ataxia, frataxin, neurologic, cardiac complications, mitochondrial biogenesis, iron-sulfur cluster synthesis, iron metabolism, antioxidant responses, mitophagy.

Cardiac Transplantation in Friedreich Ataxia

Cardiac Transplantation in Friedreich Ataxia. Yoon G, Soman T, Wilson J, George K, Mital S, Dipchand AI, McCabe J, Logan W, Kantor P. J Child Neurol 0883073812448229, first published on June 29, 2012 as doi:10.1177/0883073812448229

Keywords:  Friedreich ataxia, cardiac transplantation, left ventricular failure, dilated cardiomyopathy, neurological disease, dysarthria, weakness, mild gait impairment, limb ataxia, ethical issues.

Novel Diagnostic Paradigms for Friedreich Ataxia

Novel Diagnostic Paradigms for Friedreich Ataxia.. Brigatti KW, Deutsch EC, Lynch DR, Farmer JM., J Child Neurol 0883073812448440, first published on June 29, 2012 as doi:10.1177/0883073812448440

Keywords: Friedreich ataxia, lateral-flow immunoassay, quantify the frataxin protein, biomarker for clinical trials, gene dosage analysis.

Clinical Features of Friedreich Ataxia.

Clinical Features of Friedreich Ataxia. Martin B. Delatycki and Louise A. Corben. J Child Neurol 0883073812448230, first published on June 29, 2012 as doi:10.1177/0883073812448230

Keywords: Friedreich ataxia, FXN, central and peripheral nervous system, progressive ataxia, absent lower limb reflexes, upgoing plantar responses, peripheral sensory neuropathy, cardiomyopathy, diabetes mellitus.

Friedreich Ataxia Clinical Outcome Measures: Natural History Evaluation in 410 Participants

Friedreich Ataxia Clinical Outcome Measures: Natural History Evaluation in 410 Participants Sean R. Regner, Nicholas S. Wilcox, Lisa S. Friedman, Lauren A. Seyer, Kim A. Schadt, Karlla W. Brigatti, Susan Perlman, Martin Delatycki, George R. Wilmot, Christopher M. Gomez, Khalaf O. Bushara, Katherine D. Mathews, S. H. Subramony, Tetsuo Ashizawa, Bernard Ravina, Alicia Brocht, Jennifer M. Farmer, and David R. Lynch. J Child Neurol 0883073812448462, first published on June 29, 2012 doi:10.1177/0883073812448462

Keywords: Friedreich ataxia, ataxia, dysarthria, areflexia, large international noninterventional cohort (n = 410), Friedreich Ataxia Rating Scale.

Auditory Processing Deficits in Children With Friedreich Ataxia.

Auditory Processing Deficits in Children With Friedreich Ataxia. Rance G, Corben L, Delatycki M. J Child Neurol June 29, 2012 0883073812448963

Keywords: Friedreich ataxia, auditory neuropathy, personal FM-listening systems, auditory function tests.