Duncan E. Crombie, Martin F. Pera, Martin B. Delatycki, Alice Pébay, International Journal of Cardiology, Available online 21 March 2016, ISSN 0167-5273, doi:10.1016/j.ijcard.2016.03.040.
Here, we summarise current knowledge on experimental models in which to study FRDA cardiomyopathy, with a particular focus on the use of human pluripotent stem cells as a disease mode.
Sunday, March 27, 2016
Saturday, March 26, 2016
Gastrocnemius and soleus spasticity and muscle length in Friedreich’s ataxia
Sarah C. Milne, Louise A. Corben, Eppie Yiu, Martin B. Delatycki, Nellie Georgiou-Karistianis, Journal of Clinical Neuroscience, Available online 25 March 2016, ISSN 0967-5868, doi:10.1016/j.jocn.2016.01.011.
Gastrocnemius and soleus spasticity and contracture is apparent in people with FRDA. Spasticity is evident early in the disease and in ambulant participants. Management of spasticity and reduced muscle length should be considered in people with FRDA at disease onset to optimise function.
Gastrocnemius and soleus spasticity and contracture is apparent in people with FRDA. Spasticity is evident early in the disease and in ambulant participants. Management of spasticity and reduced muscle length should be considered in people with FRDA at disease onset to optimise function.
Friday, March 25, 2016
Letter: Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: the IMAGE-FRDA study
Ian H Harding, Parnesh Raniga, Martin B Delatycki, Monique R Stagnitti, Louise A Corben, Elsdon Storey, Nellie Georgiou-Karistianis, Gary F Egan. J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2015-312665 Published Online First: 24 March 2016
In the brain, accumulation or redistribution of iron within, and atrophy of, the cerebellar dentate nuclei have been reported.1–3 The dentate nuclei are iron-laden structures pivotal to movement coordination. However, basal ganglia and midbrain structures also have high iron content, express high levels of frataxin, and play key roles in motor regulation. Furthermore, the dentate nuclei directly innervate the thalamus and red nuclei, and indirectly project to the striatum. This biology motivates the hypothesis that iron-related pathology and/or degeneration within these extrapyramidal stations may also feature in FRDA.
In the brain, accumulation or redistribution of iron within, and atrophy of, the cerebellar dentate nuclei have been reported.1–3 The dentate nuclei are iron-laden structures pivotal to movement coordination. However, basal ganglia and midbrain structures also have high iron content, express high levels of frataxin, and play key roles in motor regulation. Furthermore, the dentate nuclei directly innervate the thalamus and red nuclei, and indirectly project to the striatum. This biology motivates the hypothesis that iron-related pathology and/or degeneration within these extrapyramidal stations may also feature in FRDA.
Establishment and Maintenance of Primary Fibroblast Repositories for Rare Diseases-Friedreich's Ataxia Example.
Li Yanjie, Polak Urszula, Clark Amanda D., Bhalla Angela D., Chen Yu-Yun, Li Jixue, Farmer Jennifer, Seyer Lauren, Lynch David, Butler Jill S., and Napierala Marek. Biopreservation and Biobanking. March 2016, ahead of print. doi:10.1089/bio.2015.0117.
We report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers.
We report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers.
Tuesday, March 22, 2016
Vivre avec la maladie de Friedreich : le vécu dysarthrique
Stéphanie Borel, Geneviève Touretz-Hermer, Sandrine Goutaland-Perrin, Peggy Gatignol. Revue Neurologique, Volume 172, Supplement 1, April 2016, Page A163, ISSN 0035-3787, doi:10.1016/j.neurol.2016.01.387.
Cette étude porte sur l’auto-évaluation du handicap de la voix et de la parole des personnes atteintes de la maladie de Friedreich (FRDA). L’utilisation du VHI et du SHI est appropriée pour mettre en évidence les différents profils dysarthriques des participants FRDA. L’utilisation conjointe de ces deux questionnaires semble inadaptée pour des raisons de durée de passation et de non-spécificité par rapport à la maladie de Friedreich. D’autres études sont nécessaires pour mieux connaître l’impact de la FRDA sur la qualité de vie des personnes atteintes, mais aussi l’outil le plus adapté pour le mesurer.
Cette étude porte sur l’auto-évaluation du handicap de la voix et de la parole des personnes atteintes de la maladie de Friedreich (FRDA). L’utilisation du VHI et du SHI est appropriée pour mettre en évidence les différents profils dysarthriques des participants FRDA. L’utilisation conjointe de ces deux questionnaires semble inadaptée pour des raisons de durée de passation et de non-spécificité par rapport à la maladie de Friedreich. D’autres études sont nécessaires pour mieux connaître l’impact de la FRDA sur la qualité de vie des personnes atteintes, mais aussi l’outil le plus adapté pour le mesurer.
Monday, March 21, 2016
A Case of Ataxia with Isolated Vitamin E Deficiency Initially Diagnosed as Friedreich's Ataxia
Michael Bonello and Partha Ray. Case Rep Neurol Med. 2016; 2016: 8342653. Published online 2016 Feb 16. doi:10.1155/2016/8342653
We advocate that vitamin E levels should form part of the initial screen for a patient with young onset progressive ataxia. In the literature there are a number of cases of patients who have been clinically diagnosed prior to genetic testing being widely available. We do recommend that such patients have their frataxin gene checked and if negative have a vitamin E blood level tested as adequate treatment with high dose vitamin E can halt progression of the condition and can be invaluable in genetic counselling.
We advocate that vitamin E levels should form part of the initial screen for a patient with young onset progressive ataxia. In the literature there are a number of cases of patients who have been clinically diagnosed prior to genetic testing being widely available. We do recommend that such patients have their frataxin gene checked and if negative have a vitamin E blood level tested as adequate treatment with high dose vitamin E can halt progression of the condition and can be invaluable in genetic counselling.
Saturday, March 19, 2016
AVC chez un patient de 25 ans atteint d’une maladie de Friedreich
Cyrielle Coignion, Cyril Goizet, Xavier Vandamme, Revue Neurologique, Volume 172, Supplement 1, April 2016, Page A124, ISSN 0035-3787, doi:10.1016/j.neurol.2016.01.293.
L’atteinte cardiaque serait responsable de 59 % des décès chez ces patients. L’idébénone pourrait avoir un effet protecteur en améliorant la fonction cardiaque. L’association maladie de Friedreich et accidents vasculaires cérébraux est possible par le biais d’une cardiomyopathie hypertrophique et d’une FA qu’il est nécessaire de dépister afin de mettre en place un traitement cardioprotecteur.
L’atteinte cardiaque serait responsable de 59 % des décès chez ces patients. L’idébénone pourrait avoir un effet protecteur en améliorant la fonction cardiaque. L’association maladie de Friedreich et accidents vasculaires cérébraux est possible par le biais d’une cardiomyopathie hypertrophique et d’une FA qu’il est nécessaire de dépister afin de mettre en place un traitement cardioprotecteur.
Both idebenone and idebenol are localized near the lipid-water interface of the membrane and increase its fluidity
Victoria Gómez-Murcia, Alejandro Torrecillas, Ana M. de Godos, Senena Corbalán-García, Juan C. Gómez-Fernández, Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1858, Issue 6, June 2016, Pages 1071-1081, ISSN 0005-2736, doi:10.1016/j.bbamem.2016.02.034.
"Idebenone is an interesting drug but care should be taken in calling it a coenzyme Q analogue."
Idebenone is sometimes assumed to be an analog of ubiquinone, although their way of interaction with the components of the electron transport chain in mitochondria differs. Whereas ubiquinone-10 carries electrons from complex I and complex II to complex III, idebenone receives electrons from complex I. idebenone shares with ubiquinone the same quinone group, it might also be expected to act as a potent antioxidant, although other studies do not exclude the idea that idebenone may detoxify ROS in a different way to ubiquinone. Since idebenone and idebenol have similar locations, this may explain why this pair does not play exactly the same role as the couple ubiquinone-10/ubiquinol-10 in the mitochondria.
"Idebenone is an interesting drug but care should be taken in calling it a coenzyme Q analogue."
Idebenone is sometimes assumed to be an analog of ubiquinone, although their way of interaction with the components of the electron transport chain in mitochondria differs. Whereas ubiquinone-10 carries electrons from complex I and complex II to complex III, idebenone receives electrons from complex I. idebenone shares with ubiquinone the same quinone group, it might also be expected to act as a potent antioxidant, although other studies do not exclude the idea that idebenone may detoxify ROS in a different way to ubiquinone. Since idebenone and idebenol have similar locations, this may explain why this pair does not play exactly the same role as the couple ubiquinone-10/ubiquinol-10 in the mitochondria.
Friday, March 18, 2016
Patent application title: MITOCHONDRIAL PROTEINS CONSTRUCTS AND USES THEREOF
Publication date: 2016-03-17 Patent application number: 20160075745
The method according to claim 19, wherein said functional protein is frataxin, respectively OTC, and said mitochondrial disorder is Friedreich's ataxia or any other disorder associated with deficiency of frataxin or with defective frataxin or, respectively, a disorder associated with a deficiency of OTC or with defective OTC.
The method according to claim 19, wherein said functional protein is frataxin, respectively OTC, and said mitochondrial disorder is Friedreich's ataxia or any other disorder associated with deficiency of frataxin or with defective frataxin or, respectively, a disorder associated with a deficiency of OTC or with defective OTC.
Thursday, March 10, 2016
New Clinical Trial: Rosuvastatin (Crestor) in Friedreich Ataxia
ClinicalTrials.gov Identifier: NCT02705547 First received: March 5, 2016
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 19103
Principal Investigator: David Lynch, MD PhD
This is an open-label study of Rosuvastatin (Crestor) in patients with FRDA. Study subjects will receive 10 mg of Rosuvastatin daily for 3 months.Daily administration of oral tablets of Rosuvastatin, 10 mg.
Context: Friedreich ataxia (FRDA) is a progressive neurodegenerative disease of children and adults for which there is presently no therapy. It has previously been reported that patients with FRDA have lower than expected HDL levels, and recent work by Dr. Blair at the University of Pennsylvania has found that serum ApoA-1 levels in FRDA patients are lower than those in controls. ApoA-1 levels are controlled by HMG-CoA activity, which is elevated in FRDA, and we hope to examine whether HMG-CoA levels can be inhibited by giving statins to patients with FRDA. Inhibition of this pathway has been proposed as a treatment for a variety of neurodegenerative disorders, and we will examine if FRDA may be one of them by looking at various biomarkers in the disease.
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 19103
Principal Investigator: David Lynch, MD PhD
This is an open-label study of Rosuvastatin (Crestor) in patients with FRDA. Study subjects will receive 10 mg of Rosuvastatin daily for 3 months.Daily administration of oral tablets of Rosuvastatin, 10 mg.
Context: Friedreich ataxia (FRDA) is a progressive neurodegenerative disease of children and adults for which there is presently no therapy. It has previously been reported that patients with FRDA have lower than expected HDL levels, and recent work by Dr. Blair at the University of Pennsylvania has found that serum ApoA-1 levels in FRDA patients are lower than those in controls. ApoA-1 levels are controlled by HMG-CoA activity, which is elevated in FRDA, and we hope to examine whether HMG-CoA levels can be inhibited by giving statins to patients with FRDA. Inhibition of this pathway has been proposed as a treatment for a variety of neurodegenerative disorders, and we will examine if FRDA may be one of them by looking at various biomarkers in the disease.
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