Tobias Mueller, Andreas Jerrentrup, Max Jakob Bauer, Hans Walter Fritsch and Juergen Rolf Schaefer. Orphanet Journal of Rare Diseases201611:81 DOI: 10.1186/s13023-016-0467-2
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
Tuesday, July 5, 2016
Secondary coenzyme Q10 deficiencies in oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders
Delia Yubero, Raquel Montero, Miguel A. Martín, Julio Montoya, Antonia Ribes, Manuela Grazina, Eva Trevisson, Juan Carlos Rodriguez-Aguilera, Iain P. Hargreaves, Leonardo Salviati, Plácido Navas, Rafael Artuch, Mitochondrion, Available online 30 June 2016, ISSN 1567-7249, http://dx.doi.org/10.1016/j.mito.2016.06.007.
Non-OXPHOS diseases may present with a CoQ deficiency, such as in multiple Acyl-CoA dehydrogenase deficiency (2 patients), apraxia with oculomotor ataxia and Friedreich’s ataxia. However, decreased levels of CoQ seemed not to be a consistent feature in some of these conditions given that patients who had the same disease were found to have both normal or reduced CoQ levels.
Non-OXPHOS diseases may present with a CoQ deficiency, such as in multiple Acyl-CoA dehydrogenase deficiency (2 patients), apraxia with oculomotor ataxia and Friedreich’s ataxia. However, decreased levels of CoQ seemed not to be a consistent feature in some of these conditions given that patients who had the same disease were found to have both normal or reduced CoQ levels.
Friday, July 1, 2016
Mitochondrial reactive oxygen species and inflammation: Molecular mechanisms, diseases and promising therapies
Alessandro Rimessi, Maurizio Previati, Federica Nigro, Mariusz R. Wieckowski, Paolo Pinton, The International Journal of Biochemistry & Cell Biology, Available online 29 June 2016, ISSN 1357-2725, Doi:10.1016/j.biocel.2016.06.015
Open Access funded by Telethon (Italy), Under a Creative Commons license
Open Access funded by Telethon (Italy), Under a Creative Commons license
Thursday, June 30, 2016
Interferon gamma may improve cardiac function in Friedreich's ataxia cardiomyopathy
Vegard Bruun Wyller, Kristine Jacobsen, Mai Britt Dahl, Hilde Nilsen, Simone Proske, Thorsten Horter, Henrik Brun, International Journal of Cardiology, Available online 29 June 2016, ISSN 0167-5273, Doi:10.1016/j.ijcard.2016.06.288
Here, we report the effect of INFγ therapy in a single patient suffering from severe FRDA cardiomyopathy. In conclusion, INFγ treatment seemed to attenuate cardiomyocyte damage and improve diastolic function in our patient. No serious side effects were registered. Thus, INFγ treatment might be a promising therapy option for FRDA hypertrophic cardiomyopathy. Results from a case report must be interpreted with great caution; ideally, a randomised controlled trial should be undertaken in order to assess the effects and safety of INFγ treatment in FRDA cardiomyopathy.
Here, we report the effect of INFγ therapy in a single patient suffering from severe FRDA cardiomyopathy. In conclusion, INFγ treatment seemed to attenuate cardiomyocyte damage and improve diastolic function in our patient. No serious side effects were registered. Thus, INFγ treatment might be a promising therapy option for FRDA hypertrophic cardiomyopathy. Results from a case report must be interpreted with great caution; ideally, a randomised controlled trial should be undertaken in order to assess the effects and safety of INFγ treatment in FRDA cardiomyopathy.
Tuesday, June 28, 2016
PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease
Juan Carlos Corona, Michael R. Duchen, Free Radical Biology and Medicine, Available online 25 June 2016, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2016.06.023.
We discuss the mechanisms underlying those beneficial effects in particular in relation to mitochondrial function, antioxidant defence, cell death and inflammation, and suggest that the PPAR-gamma agonists show significant promise as therapeutic agents in otherwise intractable neurological disease.
The effect of PPAR-gamma activation has also been studied in Friedreich’s ataxia, Pioglitazone, which seems to have fewer side effects than rosiglitazone is on a phase III clinical trial for its neuroprotective properties. The project, titled "Effect of pioglitazone administered to patients with Friedreich’s ataxia: proof of concept". However, the antecedents and possible consequences should be taken into consideration when PPAR-gamma agonist drugs are considered as possible therapeutic agents for FRDA patients.
We discuss the mechanisms underlying those beneficial effects in particular in relation to mitochondrial function, antioxidant defence, cell death and inflammation, and suggest that the PPAR-gamma agonists show significant promise as therapeutic agents in otherwise intractable neurological disease.
The effect of PPAR-gamma activation has also been studied in Friedreich’s ataxia, Pioglitazone, which seems to have fewer side effects than rosiglitazone is on a phase III clinical trial for its neuroprotective properties. The project, titled "Effect of pioglitazone administered to patients with Friedreich’s ataxia: proof of concept". However, the antecedents and possible consequences should be taken into consideration when PPAR-gamma agonist drugs are considered as possible therapeutic agents for FRDA patients.
Monday, June 27, 2016
Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration
Kuchuan Chen Guang Lin Nele A Haelterman Tammy Szu-Yu Ho Tongchao Li Zhihong Li Lita Duraine Brett H Graham Manish Jaiswal Shinya Yamamoto Matthew N Rasband Hugo J Bellen, eLife 2016; DOI:10.7554/eLife.16043
Our results indicate that an iron/sphingolipid/PDk1/Mef2 pathway may play a role in FRDA. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2)
Our results indicate that an iron/sphingolipid/PDk1/Mef2 pathway may play a role in FRDA. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2)
Sunday, June 26, 2016
Characterization of frataxin gene network in Friedreich's ataxia fibroblasts using the RNA-Seq technique
Noëlia Sanchez, Pierre Chapdelaine, Joël Rousseau, Frédéric Raymond, Jacques Corbeil, Jacques P. Tremblay, Mitochondrion, Available online 25 June 2016, ISSN 1567-7249, doi:10.1016/j.mito.2016.06.003
The study identified key players of FXN gene regulatory network and highlighted the role of FXN in the regulation of hemostasis, angiogenesis, interferon-induced apoptosis and DNA damage in FRDA. Since no efficient cure exists to treat FRDA patients, understanding the regulatory network of FXN is requisite to develop promising therapies for this debilitating condition.
This work provides valuable insight into the regulatory network of frataxin and may open new avenues for gene therapy of Friedreich's ataxia.
The study identified key players of FXN gene regulatory network and highlighted the role of FXN in the regulation of hemostasis, angiogenesis, interferon-induced apoptosis and DNA damage in FRDA. Since no efficient cure exists to treat FRDA patients, understanding the regulatory network of FXN is requisite to develop promising therapies for this debilitating condition.
This work provides valuable insight into the regulatory network of frataxin and may open new avenues for gene therapy of Friedreich's ataxia.
Saturday, June 25, 2016
Cognition in Friedreich's ataxia: a behavioral and multimodal imaging study
Dogan, I., Tinnemann, E., Romanzetti, S., Mirzazade, S., Costa, A. S., Werner, C. J., Heim, S., Fedosov, K., Schulz, S., Timmann, D., Giordano, I. A., Klockgether, T., Schulz, J. B. and Reetz, K. (2016), Annals of Clinical and Translational Neurology. doi: 10.1002/acn3.315
Open
Open
Friday, June 24, 2016
Is it your Disease or the Patient’s?
Sami L. Bahna, Alexandria Brackett, The American Journal of the Medical Sciences, Available online 24 May 2016, ISSN 0002-9629, doi:10.1016/j.amjms.2016.05.016.
When the illness has several clinical and/or laboratory features but not all features are present in every patient it is usually called a syndrome rather than a disease.
Strictly speaking, apostrophe “s” reflects possessiveness. It is correct when the syndrome or disease is named after the first described patient e.g. Lou Gehrig’s disease. Much more commonly, a syndrome or disease has been linked to the name of the physician or scientist who first described it, as an honorific eponym, e.g. Friedreich ataxia. In such instances, an apostrophe or an “s” should not be used.
When the illness has several clinical and/or laboratory features but not all features are present in every patient it is usually called a syndrome rather than a disease.
Strictly speaking, apostrophe “s” reflects possessiveness. It is correct when the syndrome or disease is named after the first described patient e.g. Lou Gehrig’s disease. Much more commonly, a syndrome or disease has been linked to the name of the physician or scientist who first described it, as an honorific eponym, e.g. Friedreich ataxia. In such instances, an apostrophe or an “s” should not be used.
Thursday, June 23, 2016
Cortico-cerebellar dysfunctions underlying executive deficits in Friedreich’s ataxia
22nd Annual Meeting of the Organization for Human Brain Mapping. Poster Session Tuesday, June 28, 2016. Imis Dogan, Eugenie Tinnemann, Sandro Romanzetti, Shahram Mirzazade, Ana Costa, Cornelius Werner, Stefan Heim, Kathrin Fedosov, Stefanie Schulz, Dagmar Timman-Braun, Ilaria Giordano, Thomas Klockgether, Jörg Schulz, Kathrin Reetz.
Neuropsychological test data provides evidence of executive impairment in individuals with FRDA, in particular pertaining to phonemic verbal fluency and social cognition. During phonological processing, the observed pattern of increased cerebellar and cortical neural response accompanied by impaired cortico-cerebellar functional coupling indicates dysfunctions in cerebro-cerebellar pathways and functional reorganization, which may be driven by disease-related cerebellar damage.
Neuropsychological test data provides evidence of executive impairment in individuals with FRDA, in particular pertaining to phonemic verbal fluency and social cognition. During phonological processing, the observed pattern of increased cerebellar and cortical neural response accompanied by impaired cortico-cerebellar functional coupling indicates dysfunctions in cerebro-cerebellar pathways and functional reorganization, which may be driven by disease-related cerebellar damage.
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