Spanish
http://mvod.lvlt.rtve.es/resources/TE_SENTREP/mp3/7/0/1460534569907.mp3
http://www.rtve.es/alacarta/audios/entre-probetas/entre-probetas-ataxia-friedreich-13-04-16/3566612/
Wednesday, April 13, 2016
Interview with Dr. Javier Diaz-Nido talking about Friedreich's Ataxia (SPA)
http://mvod.lvlt.rtve.es/resources/TE_SENTREP/mp3/7/0/1460534569907.mp3
http://www.rtve.es/alacarta/audios/entre-probetas/entre-probetas-ataxia-friedreich-13-04-16/3566612/
Italian program for independent research on drugs: 10 year follow-up of funded studies in the area of rare diseases
Giuseppe Traversa, Lucia Masiero, Luciano Sagliocca and Francesco Trotta. Orphanet Journal of Rare Diseases 2016 11:36 DOI: 10.1186/s13023-016-0420-4
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Our data suggest that adequately powered randomized trials can represent the gold standard also for rare diseases. There are also important implications for clinical practice, as can be expected by projects characterized by clinical endpoints and extensive follow-up. It is unlikely that many of these studies may have been conducted in a for profit perspective, given the absence of commercial interest.
We documented that, even though it takes time to set up and conduct a funding program for independent research, the overall results are highly rewarding. Independent funding is crucial in supporting studies aimed at answering questions that are relevant for clinical practice despite the lack of sufficient commercial interest.
OPEN ACCESS
Our data suggest that adequately powered randomized trials can represent the gold standard also for rare diseases. There are also important implications for clinical practice, as can be expected by projects characterized by clinical endpoints and extensive follow-up. It is unlikely that many of these studies may have been conducted in a for profit perspective, given the absence of commercial interest.
We documented that, even though it takes time to set up and conduct a funding program for independent research, the overall results are highly rewarding. Independent funding is crucial in supporting studies aimed at answering questions that are relevant for clinical practice despite the lack of sufficient commercial interest.
Tuesday, April 12, 2016
Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
Alexandra Essebier, Patricia Vera Wolf, Minh Duc Cao, Bernard J. Carroll, Sureshkumar Balasubramanian and Mikael Bodén, Front. Neurosci., 08 March 2016 doi:10.3389/fnins.2016.00092
Friedreich ataxia (FRDA) is a loss-of-function disease caused by an expanded intronic GAA repeat in the Frataxin (FXN) gene, and in our analysis it displayed the greatest number of epigenetic marks in its distance profile. Based on our statistical analyses of epigenetic marks around the repeat, specific hypotheses can be drawn to address this transition. For example, this is consistent with the findings that suggest that the inhibitors of histone deacetylase increase FXN expression levels. It would be interesting to assess whether blocking histone methyl transferase to prevent H3K9ac and H3K27ac would promote the stability of the GAA repeat.
Friedreich ataxia (FRDA) is a loss-of-function disease caused by an expanded intronic GAA repeat in the Frataxin (FXN) gene, and in our analysis it displayed the greatest number of epigenetic marks in its distance profile. Based on our statistical analyses of epigenetic marks around the repeat, specific hypotheses can be drawn to address this transition. For example, this is consistent with the findings that suggest that the inhibitors of histone deacetylase increase FXN expression levels. It would be interesting to assess whether blocking histone methyl transferase to prevent H3K9ac and H3K27ac would promote the stability of the GAA repeat.
Monday, April 11, 2016
Roles of Fe–S proteins: from cofactor synthesis to iron homeostasis to protein synthesis
Debkumar Pain, Andrew Dancis, Current Opinion in Genetics & Development, Volume 38, June 2016, Pages 45-51, ISSN 0959-437X, doi:10.1016/j.gde.2016.03.006.
Impairment of Fe–S cluster assembly creates diseases in diverse and surprising ways: the loss of function of lipoic acid synthase, the heme biosynthetic pathway in red cell precursors is specifically targeted and tRNA modifications arising from action of the cysteine desulfurase and/or Fe–S cluster proteins are lost. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes.
Impairment of Fe–S cluster assembly creates diseases in diverse and surprising ways: the loss of function of lipoic acid synthase, the heme biosynthetic pathway in red cell precursors is specifically targeted and tRNA modifications arising from action of the cysteine desulfurase and/or Fe–S cluster proteins are lost. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes.
Sunday, April 10, 2016
The Structure of the Complex Between Yeast Frataxin and Ferrochelatase: Characterization and pre-Steady State Reaction of Ferrous Iron Delivery and Heme Synthesis
Christopher G. Soderberg, Mallory E. Gillam, Eva-Christina Ahlgren, Gregory A. Hunter, Oleksandr Gakh, Grazia Isaya, Gloria C. Ferreira and Salam Al-Karadaghi, The Journal of biological chemistry: 2016 First Published on March 29, 2016, doi: 10.1074/jbc.M115.701128
They support the proposal that frataxin-mediated delivery of this potentially toxic substrate (Fe2+)overcomes formation of reactive oxygen species.
They support the proposal that frataxin-mediated delivery of this potentially toxic substrate (Fe2+)overcomes formation of reactive oxygen species.
Saturday, April 9, 2016
Effects of Genetic Severity on Glucose Homeostasis in Friedreich Ataxia
Charles J. Isaacs BA, Karlla W. Brigatti MS, Olena Kucheruk RN MPH, Sarah Ratcliffe PhD, Tom Sciascia MD, Shana E. McCormack MD, Steven M. Willi MD and David R. Lynch MD PhD, Muscle & Nerve, Accepted manuscript online: 7 APR 2016 DOI: 10.1002/mus.25136
Genetic severity impacts the global homeostatic profile, whereas relative contributions of insulin secretion and action vary from patient-to-patient.
Genetic severity impacts the global homeostatic profile, whereas relative contributions of insulin secretion and action vary from patient-to-patient.
Friday, April 8, 2016
Accessing the accelerated approval pathway for rare disease therapeutics
Emil D Kakkis, Sara Kowalcyk & Max G Bronstein, Nature Biotechnology 34, 380–383 (2016) doi:10.1038/nbt.3530
Improvements must be made to the qualification process for biomarkers as primary endpoints in pivotal clinical studies of treatments for the rarest of diseases.
Improvements must be made to the qualification process for biomarkers as primary endpoints in pivotal clinical studies of treatments for the rarest of diseases.
Thursday, April 7, 2016
Mouvements oculaires anormaux : aide au diagnostic étiologique/topographique en neurologie
Abnormal eye movements: Etiologic/topographic diagnostic tool in neurology / Mouvements oculaires anormaux : aide au diagnostic étiologique/topographique en neurologie
FMC, Volume 7, Issue 1, February 2016, Pages 16-24, ISSN 1878-7762, doi:10.1016/j.praneu.2015.12.003.
Acquired neurological nystagmus and other abnormal eye movements may be valuable diagnostic tools. We provide a “practical” approach, with the objective of highlighting for neurologists the importance of abnormal eye movement observation in order to improve the subtlety of clinical diagnosis.
Les nystagmus acquis centraux ou les autres types de mouvements oculaires anormaux d’origine neurologique ont pour certains une valeur séméiologique intéressante. Nous proposons une approche « pratique » visant à sensibiliser le neurologue à l’observation de mouvements oculaires anormaux pour améliorer la finesse du diagnostic clinique.
FMC, Volume 7, Issue 1, February 2016, Pages 16-24, ISSN 1878-7762, doi:10.1016/j.praneu.2015.12.003.
Acquired neurological nystagmus and other abnormal eye movements may be valuable diagnostic tools. We provide a “practical” approach, with the objective of highlighting for neurologists the importance of abnormal eye movement observation in order to improve the subtlety of clinical diagnosis.
Les nystagmus acquis centraux ou les autres types de mouvements oculaires anormaux d’origine neurologique ont pour certains une valeur séméiologique intéressante. Nous proposons une approche « pratique » visant à sensibiliser le neurologue à l’observation de mouvements oculaires anormaux pour améliorer la finesse du diagnostic clinique.
Wednesday, April 6, 2016
New tool enables scientists to interpret 'dark matter' DNA
Gladstone Institutes. "New tool enables scientists to interpret 'dark matter' DNA: Breakthrough technology opens the door to identifying new drug targets that could treat many genetic diseases." ScienceDaily. ScienceDaily, 4 April 2016. .
Scientists at the Gladstone Institutes have invented a new way to read and interpret the human genome. The computational method, called TargetFinder, can predict where non-coding DNA--the DNA that does not code for proteins--interacts with genes. This technology helps researchers connect mutations in the so-called genomic "dark matter" with the genes they affect, potentially revealing new therapeutic targets for genetic disorders.
"Our ability to predict the gene targets of enhancers so accurately enables us to link mutations in enhancers to the genes they target," said Pollard. "Having that link is the first step towards using these connections to treat diseases."
Scientists at the Gladstone Institutes have invented a new way to read and interpret the human genome. The computational method, called TargetFinder, can predict where non-coding DNA--the DNA that does not code for proteins--interacts with genes. This technology helps researchers connect mutations in the so-called genomic "dark matter" with the genes they affect, potentially revealing new therapeutic targets for genetic disorders.
"Our ability to predict the gene targets of enhancers so accurately enables us to link mutations in enhancers to the genes they target," said Pollard. "Having that link is the first step towards using these connections to treat diseases."
Tuesday, April 5, 2016
Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease
Ana Dinca, Wei-Ming Chien and Michael T. Chin. Int. J. Mol. Sci. 2016, 17(2), 263; doi:10.3390/ijms17020263
Review
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Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa).
Review
OPEN ACCESS
Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa).
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