Saturday, August 31, 2013

Energy failure—does it contribute to neurodegeneration?

Energy failure—does it contribute to neurodegeneration?. Divya Pathak, Amandine Berthet and Ken Nakamura; Annals of Neurology, Accepted manuscript online: 22 AUG 2013 04:13PM EST | DOI: 10.1002/ana.24014

Energy failure has never been directly demonstrated in affected neurons in these diseases, nor has it been proved to produce degeneration in disease models but energy failure from mitochondrial dysfunction is proposed to be a central mechanism leading to neuronal death in a range of neurodegenerative diseases.

Widespread and enzyme-independent N ε - acet ylation and N ε -succinylation of proteins in the chemical conditions of the mitochondrial matrix

Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemicalconditions of the mitochondrial matrix. Gregory R. Wagner and R. Mark Payne; J. Biol. Chem. jbc.M113.486753. First Published on August 13, 2013, doi:10.1074/jbc.M113.486753

FULL TEXT PDF

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia. Swarup, V., Srivastava, A. K., Padma, M. V. and Rajeswari, M. R.; J. Neurosci. Res.. doi: 10.1002/jnr.23262

Keywords: Friedreich's ataxia (FRDA), plasma proteins, α1-antitrypsin, apolipoprotein A-I, albumin, apolipoprotein C-II, C-III.

Friday, August 30, 2013

Iron–Sulfur Centers

Iron–Sulfur Centers: New Roles for Ancient Metal Sites. R. Grazina, S.R. Pauleta, J.J.G. Moura, I. Moura; Comprehensive Inorganic Chemistry II (Second Edition), Volume 3, 2013, Pages 103-148

Bioinorganic Neurochemistry. D.S. Folk, F. Kielar, K.J. Franz; Comprehensive Inorganic Chemistry II (Second Edition), Volume 3, 2013, Pages 207-240

Tuesday, August 27, 2013

Mitochondrial DNA Instability in Cells Lacking Aconitase Correlates with Iron Citrate Toxicity

Mitochondrial DNA Instability in Cells Lacking Aconitase Correlates with Iron Citrate Toxicity. Muhammad A. Farooq, Tammy M. Pracheil, Zhejun Dong, Fei Xiao, and Zhengchang Liu. Oxidative Medicine and Cellular Longevity, Volume 2013 (2013), Article ID 493536, 10 pages
http://dx.doi.org/10.1155/2013/493536

FULL TEXT PDF

Tuesday, August 20, 2013

Multifaceted roles of ultra-rare and rare disease patients/parents in drug discovery

Multifaceted roles of ultra-rare and rare disease patients/parents in drug discovery. Jill Wood, Lori Sames, Allison Moore, Sean Ekins. Drug Discovery Today, Available online 19 August 2013. http://dx.doi.org/10.1016/j.drudis.2013.08.006

Keywords: Advocacy; Collaboration; Crowdfunding; Drug discovery; Foundations; Hereditary diseases; Patient advocates; Patient support; Rare diseases; Translational research; Ultra-rare diseases

Monday, August 19, 2013

Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation

Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation. Provvidenza Maria Abruzzo, Marina Marini, Alessandra Bolotta, Gemma Malisardi, Stefano Manfredini, Alessandro Ghezzo, Antonella Pini, Gianluca Tasco, and Rita Casadio. BioMed Research International.

FULL TEXT PDF

Epigenetic modifications in trinucleotide repeat diseases

Epigenetic modifications in trinucleotide repeat diseases. Marguerite V. Evans-Galea, Anthony J. Hannan, Nissa Carrodus, Martin B. Delatycki, Richard Saffery. Trends in Molecular Medicine, Available online 14 August 2013

REVIEW

Systematic review of available evidence on 11 high-priced inpatient orphan drugs

Systematic review of available evidence on 11 high-priced inpatient orphan drugs. Tim A Kanters, Caroline de Sonneville-Koedoot, W Ken Redekop and Leona Hakkaart. Orphanet Journal of Rare Diseases 2013, 8:124 doi:10.1186/1750-1172-8-124.

Full text pdf

STRUCTURAL INSIGHTS INTO THE FUNCTION OF FRATAXIN

STRUCTURAL INSIGHTS INTO THE FUNCTION OF FRATAXIN . Project Information: STEMMLER, TIMOTHY LOUIS, WAYNE STATE UNIVERSITY,

An Open-label Study of the Effects of Acetyl-L-Carnitine on Cardiovascular Outcomes in Friedreich's Ataxia

An Open-label Study of the Effects of Acetyl-L-Carnitine on Cardiovascular Outcomes in Friedreich's Ataxia. ClinicalTrials.gov.

The purpose of this study is to learn how treatment with acetyl-L-carnitine (ALCAR) will affect the hearts of patients with Friedrich's Ataxia as well as how it may affect other symptoms of Friedrich's Ataxia such as difficulties with balance, walking, or upper arm function.

University of South Florida, Information provided by (Responsible Party): Theresa Zesiewicz, University of South Florida

A GAA repeat expansion reporter model of Friedreich's ataxia recapitulates the genomic context and allows rapid screening of therapeutic compounds

A GAA repeat expansion reporter model of Friedreich's ataxia recapitulates the genomic context and allows rapid screening of therapeutic compounds. Michele M.P. Lufino, Ana M. Silva2, Andrea H. Németh, Javier Alegre-Abarrategui, Angela J. Russell and Richard Wade-Martins. Hum. Mol. Genet. (2013), doi: 10.1093/hmg/ddt370

keywords: Friedreich's ataxia (FRDA), frataxin gene (FXN), cell models, GAA-expanded FXN genomic DNA reporter model, BAC vectors, luciferase.

Friday, August 9, 2013

Friedreich Ataxia: Executive Control Is Related to Disease Onset and GAA Repeat Length

Friedreich Ataxia: Executive Control Is Related to Disease Onset and GAA Repeat Length. Wolfgang Nachbauer, Thomas Bodner, Sylvia Boesch, Elfriede Karner, Andreas Eigentler, Lisa Neier, Thomas Benke, Margarete Delazer. The Cerebellum August 2013, DOI 10.1007/s12311-013-0513-8

Keywords: Friedreich ataxia (FRDA), specific cognitive impairment, GAA repeat size, age of onset, disease duration, executive functions, attention, memory, visual perception.

Wednesday, August 7, 2013

A little better than placebo is still better than nothing

A little better than placebo is still better than nothing. Adrian S Dobs. Nature Medicine 19, 962 (2013), doi:10.1038/nm0813-962
Published online 06 August 2013

While we wait for a cure, often we are faced with this situation, and we have great difficulty accessing these "light" drugs, but should exist more "specialists" with these ethical principles.

Doctors often dismiss drugs as ineffective if they fail to outperform dummy pills in randomized trials. That's a mistake. When active medicines have few side effects and produce a strong placebo effect, such drugs, even if they prove just slightly better than placebo, should be embraced for the relief they can bring to patients who have few safe alternatives.

Tuesday, August 6, 2013

Vitamin E: A Dark Horse at the Crossroad of Cancer Management

Vitamin E: A Dark Horse at the Crossroad of Cancer Management. Eduardo Cardenas, Rita Ghosh; Biochemical Pharmacology, Available online 3 August 2013

Although the paper is focused on the cancer, makes a good review of current knowledge about vitamin E, check all its isoforms, metabolism, absorption, transporters, antioxidant potency, etc..

When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources).

The Role of Mitochondria in Cellular Iron–Sulfur Protein Biogenesis: Mechanisms, Connected Processes, and Diseases

The Role of Mitochondria in Cellular Iron–Sulfur Protein Biogenesis: Mechanisms, Connected Processes, and Diseases. Oliver Stehling and Roland Lill.Cold Spring Harb Perspect Biol August 2013;5:a011312

Full text pdf

Frataxin Mutants

Frataxin Mutants. Roberto Testi; Patent US20130196932 A1,1 Ago 2013.

The invention relates to the identification of a mutant frataxin protein and methods of delivering said protein into cells.

Saturday, August 3, 2013

His86 from the N-terminus of frataxin coordinates iron and is required for Fe‒S cluster synthesis

His86 from the N-terminus of frataxin coordinates iron and is required for Fe‒S cluster synthesis. Leslie E Gentry , Matthew A Thacker , Reece Doughty , Russell Timkovich , and Laura S. Busenlehner. Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi400443n. Publication Date (Web): August 2, 2013

Friday, August 2, 2013

The effect of crowding and confinement: a comparison of Yfh1 stability in different environments

The effect of crowding and confinement: a comparison of Yfh1 stability in different environments . Domenico Sanfelice, Anastasia Politou, Stephen R Martin, Paolo De Los Rios, Pierandrea Temussi and Annalisa Pastore. 2013 Phys. Biol. 10 045002 doi:10.1088/1478-3975/10/4/045002

Repligen, Pharmacology data and biomarker activity from our Phase 1 trial in Friedreich's ataxia (FA) patients of our product candidate, RG2833,

Repligen, Pharmacology data and biomarker activity from Phase 1 trial in Friedreich's ataxia (FA) patients of the product candidate, RG2833.. Reuters, Thu Aug 1, 2013

We analyzed the pharmacology data and biomarker activity from our Phase 1 trial in Friedreich's ataxia (FA) patients of our product candidate, RG2833, a compound that interferes with the function of the histone deacetylase (HDAC) class of enzymes. The trial results show that RG2833 was well tolerated and able to improve the expression of frataxin - a disease biomarker – in a dose-dependent manner. While there were no adverse events reported, the generation of potentially toxic metabolites was observed. Overall, the Phase 1 results support the use of an oral HDAC inhibitor in the treatment of FA, however we believe that other compounds in our HDAC inhibitor portfolio may be more suitable than RG2833 for clinical development. Consistent with our focus on bioprocessing, we are seeking non-profit and biopharmaceutical development partners to support future development.

Thursday, August 1, 2013

Mitochondrial Ferritin in Neurodegenerative Diseases

Mitochondrial Ferritin in Neurodegenerative Diseases. Hongkuan Yang, Mingchun Yang, Hongpeng Guan, Ziyi Liu, Shiguang Zhao, Shigeko Takeuchi, Daijiro Yanagisawa, Ikuo Tooyama. Neuroscience Research, Available online 31 July 2013. DOI: http://dx.doi.org/10.1016/j.neures.2013.07.005

Keywords: Mitochondrial ferritin (FtMt), testis and the brain, neurodegenerative diseases, Alzheimer's disease, restless legs syndrome, Parkinson's disease, age-related macular degeneration (AMD), Friedreich's ataxia, frataxin, neuroprotective role.