Rosita Shishegar, Ian H. Harding, Louise A. Corben, Martin B. Delatycki, Elsdon Storey, Gary F. Egan, Nellie Georgiou-Karistianis; Cerebellum (2020). doi:10.1007/s12311-019-01094-6
These findings provide the first evidence of increased longitudinal activation over time in the cerebral cortex in FRDA, compared with controls, despite comparable working memory performance. This finding represents a possible compensatory response in the ventral attention network to help sustain working memory performance in individuals with FRDA.
Friday, January 3, 2020
Sunday, December 29, 2019
Health related quality of life in Friedreich Ataxia in a large heterogeneous cohort
Emily Xiong, Abigail E. Lynch, Louise A. Corben, Martin B. Delatycki, S.H. Subramony, Khalaf Bushara, Christopher M. Gomez, J. Chad Hoyle, Grace Yoon, Bernard Ravina, Katherine D. Mathews, George Wilmot, Theresa Zesiewicz, M. Susan Perlman, Jennifer M. Farmer, Christian Rummey, David R. Lynch; Neurological Sciences, Volume 0, Issue 0, 116642 DOI:10.1016/j.jns.2019.116642
The SF-36 and symptom specific scales capture dysfunction in FRDA in a manner that reflects disease status. HRQOL dysfunction was greatest on physically related scales; such scales correlated with disease duration, indicating that they worsen with progressing disease.
The SF-36 and symptom specific scales capture dysfunction in FRDA in a manner that reflects disease status. HRQOL dysfunction was greatest on physically related scales; such scales correlated with disease duration, indicating that they worsen with progressing disease.
Friday, December 27, 2019
Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia
Mariana Igoillo-Esteve, Ana F. Oliveira, Cristina Cosentino, Federica Fantuzzi, Céline Demarez, Sanna Toivonen, Amélie Hu, Satyan Chintawar, Miguel Lopes, Nathalie Pachera, Ying Cai, Baroj Abdulkarim, Myriam Rai, Lorella Marselli, Piero Marchetti, Mohammad Tariq, Jean-Christophe Jonas, Marina Boscolo, Massimo Pandolfo, Décio L. Eizirik, and Miriam Cnop; JCI Insight. Published December 26, 2019. doi:10.1172/jci.insight.134221.
Thursday, December 26, 2019
Antioxidant-mediated protective role of Hericium erinaceus (Bull.: Fr.) Pers. against oxidative damage in fibroblasts from Friedreich’s ataxia patient
LEW, Sze-Yuen; YOW, Yoon-Yen; LIM, Lee-Wei; WONG, Kah-Hui; SciELO journals. Dataset doi:10.6084/m9.figshare.11390835.v1
In this study, we investigated the antioxidant activities of a standardized aqueous extract from fruiting bodies of Hericium erinaceus mushroom (HESAE) and its protective effects against oxidative damage induced by L-Buthionine sulfoximine (BSO) in fibroblasts derived from FRDA patient. The lactate dehydrogenase-based viability assay showed that FRDA fibroblast was sensitive to 12.5 mM BSO with a reduction of viability to 52.51 ± 13.92% after 24 h of BSO exposure. Interestingly, co-incubation with 32 mg/mL HESAE increased the viability to 85.35 ± 3.4%. Further, 12.5 mM BSO caused a decrease in the ratio of cellular reduced glutathione (GSH) to oxidised GSH (GSSG) that leads to cell death.
FJ
In this study, we investigated the antioxidant activities of a standardized aqueous extract from fruiting bodies of Hericium erinaceus mushroom (HESAE) and its protective effects against oxidative damage induced by L-Buthionine sulfoximine (BSO) in fibroblasts derived from FRDA patient. The lactate dehydrogenase-based viability assay showed that FRDA fibroblast was sensitive to 12.5 mM BSO with a reduction of viability to 52.51 ± 13.92% after 24 h of BSO exposure. Interestingly, co-incubation with 32 mg/mL HESAE increased the viability to 85.35 ± 3.4%. Further, 12.5 mM BSO caused a decrease in the ratio of cellular reduced glutathione (GSH) to oxidised GSH (GSSG) that leads to cell death.
FJ
Tuesday, December 24, 2019
Rating scales for rare neurological diseases
Massimo Pandolfo; Neurol Genet Dec 2019, 5 (6) e380; DOI: 10.1212/NXG.0000000000000380
While only future experience will establish whether these scales are equally effective in FRDA clinical trials or if one proves superior, the point that they are both ataxia rating scales rather than comprehensive assessments of all FRDA neurologic features remains. Can we generalize this conclusion and say that rating scales assessing specific neurologic features are to be preferred to disease-specific scales in rare neurologic disorders? This is an open and controversial question. There have been and there are continuing efforts to develop and validate disease-specific scales for rare and even ultra-rare diseases, with the goal of disposing of robust, sensitive outcome measures for clinical trials, capturing as much as possible of the complexities of each of these conditions. Whether the same goal can be attained by appropriately combining general scales for neurologic impairments as weakness, spasticity, ataxia, and dystonia remains to be determined, but, in the light of our experience with a disease with as complex a neurologic picture as FRDA, this approach may be a viable and possibly even a preferable option.
While only future experience will establish whether these scales are equally effective in FRDA clinical trials or if one proves superior, the point that they are both ataxia rating scales rather than comprehensive assessments of all FRDA neurologic features remains. Can we generalize this conclusion and say that rating scales assessing specific neurologic features are to be preferred to disease-specific scales in rare neurologic disorders? This is an open and controversial question. There have been and there are continuing efforts to develop and validate disease-specific scales for rare and even ultra-rare diseases, with the goal of disposing of robust, sensitive outcome measures for clinical trials, capturing as much as possible of the complexities of each of these conditions. Whether the same goal can be attained by appropriately combining general scales for neurologic impairments as weakness, spasticity, ataxia, and dystonia remains to be determined, but, in the light of our experience with a disease with as complex a neurologic picture as FRDA, this approach may be a viable and possibly even a preferable option.
Monday, December 23, 2019
Nanoscopic X‐ray imaging and quantification of the iron cellular architecture within single fibroblasts of Friedreich's ataxia patients
De Samber, B., Vanden Berghe, T., Meul, E., Bauters, S., Seyrich, M., Smet, J., De Paepe, B., da Silva, J.C., Bohic, S., Cloetens, P., Van Coster, R., Vandenabeele, P. and Vincze, L. (2020), J. Synchrotron Rad.. doi:10.1107/S1600577519015510
Here the nanoscale iron distribution within single fibroblasts from FRDA patients was investigated using synchrotron‐radiation‐based nanoscopic X‐ray fluorescence and X‐ray in‐line holography at the ID16A nano‐imaging beamline of the ESRF.
Various micrometre‐sized iron‐rich organelles could be revealed for the first time, tentatively identified as endoplasmic reticulum, mitochondria and lysosomes. Also a multitude of nanoscopic iron hot‐spots were observed in the cytosol, interpreted as chaperoned iron within the fibroblast's labile iron pool. These observations enable new hypotheses on the storage and trafficking of iron in the cell and ultimately to a better understanding of iron‐storage diseases such as Friedreich's ataxia.
Here the nanoscale iron distribution within single fibroblasts from FRDA patients was investigated using synchrotron‐radiation‐based nanoscopic X‐ray fluorescence and X‐ray in‐line holography at the ID16A nano‐imaging beamline of the ESRF.
Various micrometre‐sized iron‐rich organelles could be revealed for the first time, tentatively identified as endoplasmic reticulum, mitochondria and lysosomes. Also a multitude of nanoscopic iron hot‐spots were observed in the cytosol, interpreted as chaperoned iron within the fibroblast's labile iron pool. These observations enable new hypotheses on the storage and trafficking of iron in the cell and ultimately to a better understanding of iron‐storage diseases such as Friedreich's ataxia.
Sunday, December 22, 2019
Age of onset determines intrinsic functional brain architecture in Friedreich ataxia
Naeije, G., Wens, V., Coquelet, N., Sjøgård, M., Goldman, S., Pandolfo, M. and De Tiège, X.P. (2019). Ann Clin Transl Neurol. doi:10.1002/acn3.50966
Age of symptoms onset is a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptoms onset supports compensatory mechanisms for FRDA‐related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.
Age of symptoms onset is a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptoms onset supports compensatory mechanisms for FRDA‐related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.
Saturday, December 21, 2019
Psychometric properties of the Friedreich Ataxia Rating Scale
Christian Rummey, Louise A. Corben, Martin B. Delatycki, S.H. Subramony, Khalaf Bushara, Christopher M. Gomez, Joseph Chad Hoyle, Grace Yoon, Bernard Ravina, Katherine D. Mathews, George Wilmot, Theresa Zesiewicz, Susan Perlman, Jennifer M. Farmer, David R. Lynch; Neurol Genet Dec 2019, 5 (6) 371; DOI: 10.1212/NXG.0000000000000371
A correlation-based psychometric analysis of the neurologic FARSn score justifies the overall validity of the scale. In addition, omission of items of limited functional significance as created in the mFARS improves the features of the measures. Such information is crucial to the ongoing application of the mFARS in natural history studies and clinical trials. Additional analyses of longitudinal changes will be necessary to fully ascertain its utility, especially in nonambulant patients.
A correlation-based psychometric analysis of the neurologic FARSn score justifies the overall validity of the scale. In addition, omission of items of limited functional significance as created in the mFARS improves the features of the measures. Such information is crucial to the ongoing application of the mFARS in natural history studies and clinical trials. Additional analyses of longitudinal changes will be necessary to fully ascertain its utility, especially in nonambulant patients.
Friday, December 20, 2019
A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich’s ataxia
Tommaso Vannocci, Simone Dinarelli, Marco Girasole, Annalisa Pastore & Giovanni Longo; Sci Rep 9, 19282 (2019) doi:10.1038/s41598-019-55799-z
Accordingly, the disease starts appearing when the frataxin levels are below 30% those of healthy controls and are 10–35% the normal levels in FRDA patients. On the other hand, it was found that frataxin overexpression is not a solution as a therapeutic strategy: overexpression seems to be as toxic as its partial depletion. This observation is perfectly coherent with the current hypothesis that frataxin functions as a regulator of the process of conversion of cysteine into alanine through interaction with the desulfurase central to the machine of the iron sulfur cluster biogenesis machine.
Accordingly, the disease starts appearing when the frataxin levels are below 30% those of healthy controls and are 10–35% the normal levels in FRDA patients. On the other hand, it was found that frataxin overexpression is not a solution as a therapeutic strategy: overexpression seems to be as toxic as its partial depletion. This observation is perfectly coherent with the current hypothesis that frataxin functions as a regulator of the process of conversion of cysteine into alanine through interaction with the desulfurase central to the machine of the iron sulfur cluster biogenesis machine.
Thursday, December 19, 2019
Electrophysiological evidence for limited progression of the proprioceptive impairment in Friedreich ataxia
G. Naeije, M. Bourguignon, V. Wens, B. Marty, S. Goldman, R. Hari, V. Jousmäki, M. Pandolfo, X. De Tiège; Clinical Neurophysiology, 2019, Doi: 10.1016/j.clinph.2019.10.021
In any case, our study, using an objective follow-up of upper limb spino-cortical proprioceptive function in FRDA patients, pro- vides additional empirical evidence suggesting limited progressiv- ity of an early established patrhology of dorsal columns and DRG.
In any case, our study, using an objective follow-up of upper limb spino-cortical proprioceptive function in FRDA patients, pro- vides additional empirical evidence suggesting limited progressiv- ity of an early established patrhology of dorsal columns and DRG.
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