Wednesday, May 29, 2013

The balancing act of DNA repeat expansions

The balancing act of DNA repeat expansions. Jane C Kim, Sergei M Mirkin; Current Opinion in Genetics & Development, Available online 29 May 2013, http://dx.doi.org/10.1016/j.gde.2013.04.009,

Keywords: repeat expansions, replication, repair, recombination, transcription.

Friedreich's ataxia associated with subaortic membrane : A rare case.

Friedreich's ataxia associated with subaortic membrane : A rare case. Doğan A, Aksoy H, Simşek H., Herz. 2013 May 29.

No Abstract

Tuesday, May 28, 2013

An Optimized Pyrimidinol Multifunctional Radical Quencher

An Optimized Pyrimidinol Multifunctional Radical Quencher. Omar M. Khdour , Pablo M. Arce , Basab Roy , and Sidney M. Hecht; ACS Med. Chem. Lett., Just Accepted Manuscript, DOI: 10.1021/ml400130z, Publication Date (Web): May 28, 2013

Keywords: aza analogues (4-9) of idebenone, to attenuate oxidative stress, Friedreich’s ataxia (FRDA), mitochondrial and neurodegenerative diseases, FRDA, Alzheimer's disease.

Facile Electrochemical Biosensor Based on a New Bifunctional Probe for Label-Free Detection of CGG Trinucleotide Repeat

Facile Electrochemical Biosensor Based on a New Bifunctional Probe for Label-Free Detection of CGG Trinucleotide Repeat. Hanping He, Jingping Xia, Xiaoqian Peng, Gang Chang, Xiuhua Zhang, Yafen Wang, Kazuhiko Nakatani, Zhaowen Lou, Shengfu Wang. Biosensors and Bioelectronics, Available online 28 May 2013, http://dx.doi.org/10.1016/j.bios.2013.05.022

The strategy should have significant potential for the development of versatile and low-cost biosensor for early diagnosis and treatment of neurodegenerative diseases associated with trinucleotide repeats.

Keywords: Electrochemical biosensor, Trinucleotide repeat, Ferrocenyl modified naphthyridine derivative,

A NEURONAL MODEL OF NEURODEGENERATIVE DISEASE: OXIDATIVE STRESS IN THE AXONAL DAMAGE.

A NEURONAL MODEL OF NEURODEGENERATIVE DISEASE: OXIDATIVE STRESS IN THE AXONAL DAMAGE. Emanuela Piermarini, Barbara Carletti, Giulia Tozzi, Lorena Travaglini, Anna Pastore, Alessandra Torraco, Enrico Bertini and Fiorella Piemonte. RIUNIONI SCIENTIFICHE SULLA RICERCA BIOMEDICA DELL’OSPEDALE PEDIATRICO BAMBINO GESU’ E DELL’UNIVERSITA’ ROMA TRE
Martedì 28 Maggio 2013 “Stress ossidativo e patologie correlate”

Keywords: Neurons, oxidative stress, axonal damage, neuronal cell models, Friedreich’s Ataxia (FRDA), ate this neuronal cell model, shRNA lentiviral vector, axonal pathological profile of FRDA, reduced glutathione.

Friday, May 24, 2013

Increased prevalence of sleep-disordered breathing in Friedreich ataxia.

Increased prevalence of sleep-disordered breathing in Friedreich ataxia. Corben LA, Ho M, Copland J, Tai G, Delatycki MB.; Neurology. 2013 May 22. doi: 10.1212/WNL.0b013e318297ef18

Keywords: sleep-disordered breathing (SDB), Epworth Sleepiness Scale, obstructive sleep apnea syndrome.

High-dose thiamine improves the symptoms of Friedreich's ataxia

High-dose thiamine improves the symptoms of Friedreich's ataxia. Antonio Costantini, Rafaela Giorgi, Sonia D'Agostino, Maria Immacolata Pala. BMJ Case Reports 2013; doi:10.1136/bcr-2013-009424

Keywords: Friedreich's ataxia (FRDA), thiamine deficiency.

Tuesday, May 21, 2013

Iron-Sulfur Cluster Proteins Discussion Meeting 2013

Iron-Sulfur Cluster Proteins Discussion Meeting 2013. NIMR 19 April.

The meeting attracts excellent scientists from across the UK and the world and provides a great forum for informal discussions on topics related to iron-sulfur cluster structure, function, evolution and biogenesis. Annalisa Pastore

Program and abstracts

Perceived Effectiveness and Barriers to Physical Therapy Services for Families and Children With Friedreich Ataxia.

Perceived Effectiveness and Barriers to Physical Therapy Services for Families and Children With Friedreich Ataxia. Maring, Joyce PT, DPT, EdD; Croarkin, Earllaine PT, NCS; Morgan, Sylvia PT, DPT; Plack, Margaret PT, EdD.; Pediatr Phys Ther. 2013 May 16. doi: 10.1097/PEP.0b013e31828ed7cb

Keywords:physical therapy interventions, Friedreich ataxia (FA), barriers to therapy.

Saturday, May 18, 2013

RG2833 is Well-Tolerated and Increases Frataxin Gene Activity

RG2833 is Well-Tolerated and Increases Frataxin Gene Activity. by Amy Madsen on May 17, 2013, Quest Magazine Online (MDA)


Article Highlights:

-Interim results from a clinical trial of RG2833 in people with Friedreich’s ataxia (FA) show that the experimental drug is well-tolerated, and that it appears to act by increasing frataxin gene activity (frataxin protein deficiency is the cause of FA).
-The main aim of the ongoing trial is to assess the safety of RG2833 in people with FA.
-Through its translational research program, MDA has awarded Repligen two grants, totaling more than $1.7 million, to fund development of RG2833 for FA.
-While the encouraging results are an important step forward in finding new drugs, Repligen's Jim Rusche said more tests will be required before a drug like this can be available as a safe and effective treatment for FA.

A Novel PGC-1α Isoform in Brain Localizes to Mitochondria and Associates with PINK1 and VDAC

A Novel PGC-1α Isoform in Brain Localizes to Mitochondria and Associates with PINK1 and VDAC. Joungil Choi, Vera Venkatanaresh Kumar Batchu, Manfred Schubert, Rudolph J. Castellani, James W. Russell. Biochemical and Biophysical Research Communications, Available online 17 May 2013.

Down-regulation of PGC-1α is associated with mitochondrial dysfunction and impaired lipid metabolism in obesity and diabetes both of which increases the risk of neurodegenerative diseases. Down-regulation of PGC-1α also have been reported in Friedreich's ataxia.

Development of Frataxin Gene Expression Measures for the Evaluation of Experimental Treatments in Friedreich’s Ataxia

Development of Frataxin Gene Expression Measures for the Evaluation of Experimental Treatments in Friedreich’s Ataxia . Heather L. Plasterer, Eric C. Deutsch, Matthew Belmonte, Elizabeth Egan, David R. Lynch, James R. Rusche; PLoS ONE 8(5): e63958. doi:10.1371/journal.pone.0063958

Conclusions/Significance

Our data support the use of frataxin as a biomarker of drug effect. Frataxin levels are stable over time and as such a 1.5 to 2-fold change would be detectable over normal biological fluctuations. Additionally, our data support buccal cells or PBMCs as sources for measuring frataxin protein in therapeutic trials.

Friday, May 17, 2013

[2Fe-2S]-Ferredoxin binds directly to cysteine desulfurase and supplies an electron for iron-sulfur cluster assembly but is displaced by the scaffold protein or bacterial frataxin

[2Fe-2S]-Ferredoxin binds directly to cysteine desulfurase and supplies an electron for iron-sulfur cluster assembly but is displaced by the scaffold protein or bacterial frataxin. Jin Hae Kim , Ronnie O. Frederick , Nichole M. Reinen , Andrew T. Troupis , and John Lute Markley. J. Am. Chem. Soc., DOI: 10.1021/ja401950a

Keywords: Escherichia coli, [2Fe-2S]-ferredoxin (Fdx), iron-sulfur cluster biogenesis, IscU, and CyaY (bacterial frataxin).

Epigenetic mechanisms governing the process of neurodegeneration

Epigenetic mechanisms governing the process of neurodegeneration. Irfan A. Qureshi, Mark F. Mehler; Molecular Aspects of Medicine, Volume 34, Issue 4, July–August 2013, Pages 875-882. http://dx.doi.org/10.1016/j.mam.2012.06.011

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

From Mutation Identification to Therapy: Discovery and Origins of the First Approved Gene Therapy in the Western World

From Mutation Identification to Therapy: Discovery and Origins of the First Approved Gene Therapy in the Western World . John J.P. Kastelein, Colin J.D. Ross, and Michael R. Hayden. Human Gene Therapy. May 2013, 24(5): 472-478. doi:10.1089/hum.2013.063.

We hope soon have one similar paper for Friedreich's ataxia ....

Wednesday, May 15, 2013

Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial.

Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial. Arpa J, Sanz-Gallego I, Rodríguez-de-Rivera FJ, Domínguez-Melcón FJ, Prefasi D, Oliva-Navarro J, Moreno-Yangüela M.; Acta Neurol Scand. 2013 May 14. doi: 10.1111/ane.12141.

The triple therapy results seem to indicate some uncertain benefit on the neurological and heart functions in the FRDA.

Monday, May 13, 2013

New evidence for therapies in stroke rehabilitation.

New evidence for therapies in stroke rehabilitation. Dobkin BH, Dorsch A.; Curr Atheroscler Rep. 2013 Jun;15(6):331. doi: 10.1007/s11883-013-0331-y.

Recent clinical trials provide evidence for a range of new interventions to manage walking, reach and grasp, aphasia, visual field loss, and hemi-inattention.

Wednesday, May 8, 2013

Repligen HDAC inhibitors progress

5/7/13 - REPLIGEN CORP - 10-Q - MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS . http://www.pharmacychoice.com

Our third clinical development program was targeted at Friedrich's Ataxia and led by RG2833, a class I histone deacetylase ("HDAC") inhibitor. RG2833 has received Orphan Drug designation from the FDA and European Commission. We initiated a single, ascending dose Phase 1 study of RG2833 in Friedreich's Ataxia patients in Italy in the fourth quarter of 2012 and completed the patient dosing in the quarter ended March 31, 2013. We believe the results of this trial, which we are currently analyzing, may be an important consideration for any third-party that may wish to pursue a development or commercialization agreement with us for RG2833. We expect that any additional development activities that we may pursue in the future will be largely supported by sponsors or collaborators.



Tuesday, May 7, 2013

Fatigue is frequent and multifactorial in Friedreich's ataxia

Fatigue is frequent and multifactorial in Friedreich's ataxia. Cynthia B. da Silva, Camila F. Chevis, Anelyssa D'Abreu, Iscia Lopes-Cendes, Marcondes C. França Jr.; Parkinsonism & Related Disorders, Available online 7 May 2013. http://dx.doi.org/10.1016/j.parkreldis.2013.04.007

Keywords: Friedreich's ataxia, Depression, Fatigue, Sleep disorders.

Non-Viral Gene Therapy Vectors Carrying Genomic Constructs

Non-Viral Gene Therapy Vectors Carrying Genomic Constructs

George Kotzamanis, Hassan Abdulrazzak, Athanassios Kotsinas and Vassilis G. Gorgoulis (2011). Non-Viral Gene Therapy Vectors Carrying Genomic Constructs, Non-Viral Gene Therapy, Prof. Xubo Yuan (Ed.), ISBN: 978-953-307-538-9, InTech, DOI: 10.5772/19225. Available from: http://www.intechopen.com/books/non-viral-gene-therapy/non-viral-gene-therapy-vectors-carrying-genomic-constructs

Good book to understand a little more the basics of this promising technique

This book focuses on recent advancement of gene delivery systems research. With the multidisciplinary contribution in gene delivery, the book covers several aspects in the gene therapy development: various gene delivery systems, methods to enhance delivery, materials with modification and multifunction for the tumor or tissue targeting. This book will help molecular biologists gain a basic knowledge of gene delivery vehicles, while drug delivery scientist will better understand DNA, molecular biology, and DNA manipulation



Monday, May 6, 2013

Entrevista a Javier Díaz-Nido


Radio interview to Javier Diaz-Nido, Spanish Researcher on Friedreich's Ataxia
(Spanish)

Manuel Seara ha hablado sobre ataxia con Javier Díaz-Nido en el programa A hombros de gigantes de RNE, profesor titular de Biología Molecular de la Universidad Autónoma de Madrid y experto en la ataxia de Friedreich.

http://www.rtve.es/alacarta/audios/a-hombros-de-gigantes/hombros-gigantes-entrevista-javier-diaz-nido/1803448/

Sunday, May 5, 2013

Thursday, May 2, 2013

Radial diffusivity in the cerebellar peduncles correlates with clinical severity in Friedreich ataxia

Radial diffusivity in the cerebellar peduncles correlates with clinical severity in Friedreich ataxia. Christian Clemm von Hohenberg, Michael F. Schocke, Marlene C. Wigand, Wolfgang Nachbauer, Charles RG Guttmann, Marek Kubicki, Martha E. Shenton, Sylvia Boesch, Karl Egger.
Neurological Sciences, May 2013. DOI 10.1007/s10072-013-1402-0

Keywords: Friedreich ataxia, Magnetic resonance imaging, Diffusion-tensor imaging, Tract-based spatial statistics, Cerebellar peduncle, Biomarker.

Wednesday, May 1, 2013

Heme Levels Are Increased in Human Failing Hearts

Heme Levels Are Increased in Human Failing Hearts. Arineh Khechaduri, MS; Marina Bayeva, PhD; Hsiang-Chun Chang, BA; Hossein Ardehali, MD, PhD.;
J Am Coll Cardiol. 2013;61(18):1884-1893. doi:10.1016/j.jacc.2013.02.012

Similarly, aggregation of iron inside the mitochondria has been observed in the hearts of Friedreich’s ataxia patients, who develop progressive and lethal cardiac dysfunction. Thus, maintenance of iron balance inside the heart appears to be critical for its function, but it remains unknown how iron regulation is altered in failing human hearts.