Tslil Ast, Joshua D. Meisel, Shachin Patra, Gary Ruvkun, David P. Barondeau, Vamsi K. Mootha; Cell , Volume 0 , Issue 0, Published: April 25, 2019, DOI:10.1016/j.cell.2019.03.045
Fe-S clusters and is considered to be essential for viability. Here we report that when grown in 1% ambient O 2, FXN null yeast, human cells, and nematodes are fully viable. In human cells, hypoxia restores steady-state levels of Fe-S clusters and normalizes ATF4, NRF2, and IRP2 signaling events associated with FRDA. Cellular studies and in vitro reconstitution indicate that hypoxia acts through HIF-independent mechanisms that increase bioavailable iron as well as directly activate Fe-S synthesis. In a mouse model of FRDA, breathing 11% O 2 attenuates the progression of ataxia, whereas breathing 55% O 2 hastens it. Our work identifies oxygen as a key environmental variable in the pathogenesis associated with FXN depletion, with important mechanistic and therapeutic implications.
Friday, April 26, 2019
Thursday, April 25, 2019
Brain signals translated into speech using artificial intelligence
Nature news, 24 APRIL 2019 . Giorgia Guglielmi. "Technology could one day be used to help people who can’t talk to communicate".
In an effort to provide a voice for people who can’t speak, neuroscientists have designed a device that can transform brain signals into speech.
Two examples of a participant reading a sentence, followed by the synthesized version of the sentence generated from their brain activity.
In an effort to provide a voice for people who can’t speak, neuroscientists have designed a device that can transform brain signals into speech.
Two examples of a participant reading a sentence, followed by the synthesized version of the sentence generated from their brain activity.
Speech synthesis from neural decoding of spoken sentences
Gopala K. Anumanchipalli, Josh Chartier & Edward F. Chang ; Nature volume 568, pages 493–498 (2019) doi:10.1038/s41586-019-1119-1
Technology that translates neural activity into speech would be transformative for people who are unable to communicate as a result of neurological impairments. Decoding speech from neural activity is challenging because speaking requires very precise and rapid multi-dimensional control of vocal tract articulators. Here we designed a neural decoder that explicitly leverages kinematic and sound representations encoded in human cortical activity to synthesize audible speech. Recurrent neural networks first decoded directly recorded cortical activity into representations of articulatory movement, and then transformed these representations into speech acoustics. In closed vocabulary tests, listeners could readily identify and transcribe speech synthesized from cortical activity. Intermediate articulatory dynamics enhanced performance even with limited data. Decoded articulatory representations were highly conserved across speakers, enabling a component of the decoder to be transferrable across participants. Furthermore, the decoder could synthesize speech when a participant silently mimed sentences. These findings advance the clinical viability of using speech neuroprosthetic technology to restore spoken communication.
Technology that translates neural activity into speech would be transformative for people who are unable to communicate as a result of neurological impairments. Decoding speech from neural activity is challenging because speaking requires very precise and rapid multi-dimensional control of vocal tract articulators. Here we designed a neural decoder that explicitly leverages kinematic and sound representations encoded in human cortical activity to synthesize audible speech. Recurrent neural networks first decoded directly recorded cortical activity into representations of articulatory movement, and then transformed these representations into speech acoustics. In closed vocabulary tests, listeners could readily identify and transcribe speech synthesized from cortical activity. Intermediate articulatory dynamics enhanced performance even with limited data. Decoded articulatory representations were highly conserved across speakers, enabling a component of the decoder to be transferrable across participants. Furthermore, the decoder could synthesize speech when a participant silently mimed sentences. These findings advance the clinical viability of using speech neuroprosthetic technology to restore spoken communication.
Erythropoietin and Friedreich Ataxia: Time for a Reappraisal?
Boesch S and Indelicato E (2019); Front. Neurosci. 13:386. doi: 10.3389/fnins.2019.00386
Despite several clinical trials in the past, no treatment is available for the treatment of FRDA. Current lines of research focus on gene therapy, frataxin replacement strategies and on regulation of key metabolic checkpoints such as NrF2. Due to potential crosstalk with all these mechanisms, interventions on the EPO pathway still represent a valuable research field. The recent development of small EPO mimetics which maintain cytoprotective properties without erythropoietic action may open a new era in EPO research for the treatment of FRDA.
Despite several clinical trials in the past, no treatment is available for the treatment of FRDA. Current lines of research focus on gene therapy, frataxin replacement strategies and on regulation of key metabolic checkpoints such as NrF2. Due to potential crosstalk with all these mechanisms, interventions on the EPO pathway still represent a valuable research field. The recent development of small EPO mimetics which maintain cytoprotective properties without erythropoietic action may open a new era in EPO research for the treatment of FRDA.
Tuesday, April 23, 2019
A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich's Ataxia in Male and Female Patients (FRAMES)
ClinicalTrials.gov Identifier: NCT03917225.
Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophisyiological, and Clinical Markers in Patients With Friedreich's Ataxia.
Sponsor: Minoryx Therapeutics, S.L.
Locations
Belgium
Hôpital Erasme-ULB Not yet recruiting
Brussels, Belgium, B-1070
Contact: Prof. Massimo Pandolfo
France
ICM, Groupe Hospitalier Pitié Salpêtrière Not yet recruiting
Paris, France, 75646
Contact: Prof. Alexandra Durr
Germany
Universitätsklinikum RWTH Not yet recruiting
Aachen, Germany, 52074
Contact: Prof. Jörg B Schulz
Spain
Hospital Sant Joan de Déu Not yet recruiting
Barcelona, Spain
Contact: Dr. Alejandra Darling
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Dr. Francisco Javier Rodríguez de Rivera
Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophisyiological, and Clinical Markers in Patients With Friedreich's Ataxia.
Sponsor: Minoryx Therapeutics, S.L.
Locations
Belgium
Hôpital Erasme-ULB Not yet recruiting
Brussels, Belgium, B-1070
Contact: Prof. Massimo Pandolfo
France
ICM, Groupe Hospitalier Pitié Salpêtrière Not yet recruiting
Paris, France, 75646
Contact: Prof. Alexandra Durr
Germany
Universitätsklinikum RWTH Not yet recruiting
Aachen, Germany, 52074
Contact: Prof. Jörg B Schulz
Spain
Hospital Sant Joan de Déu Not yet recruiting
Barcelona, Spain
Contact: Dr. Alejandra Darling
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Dr. Francisco Javier Rodríguez de Rivera
Association between restless legs syndrome and other movement disorders
Hortensia Alonso-Navarro, Elena García-Martín, José A.G. Agúndez, View ORCID ProfileFélix Javier Jiménez-Jiménez; Neurology. 2019 Apr 19. pii: 10.1212/WNL.0000000000007500. doi: 10.1212/WNL.0000000000007500.
Review of PubMed from 1966 to September 2018 and identification of references of interest for the topic. A meta-analysis of eligible studies on the frequency of RLS in patients with PD and controls using Meta-DiSc1.1.1 software and using the PRISMA guidelines was performed.
Several studies have also suggested that RLS could be an early clinical feature of PD. RLS symptoms are frequent in multiple system atrophy, essential tremor, Tourette syndrome, Friedreich ataxia, and spinocerebellar ataxia type 3 as well.
Review of PubMed from 1966 to September 2018 and identification of references of interest for the topic. A meta-analysis of eligible studies on the frequency of RLS in patients with PD and controls using Meta-DiSc1.1.1 software and using the PRISMA guidelines was performed.
Several studies have also suggested that RLS could be an early clinical feature of PD. RLS symptoms are frequent in multiple system atrophy, essential tremor, Tourette syndrome, Friedreich ataxia, and spinocerebellar ataxia type 3 as well.
Friday, April 12, 2019
Mechanism of frataxin “bypass” in human iron-sulfur cluster biosynthesis with implications for Friedreich’s ataxia
Deepika Das, Shachin Patra, Jennifer Bridwell-Rabb, and David P. Barondeau; J. Biol. Chem. jbc.RA119.007716. doi:10.1074/jbc.RA119.007716
These results reveal an unexpected mechanism that replaces FXN-based stimulation of the Fe-S cluster biosynthetic pathway and suggest new strategies to overcome the loss of cellular FXN that may be relevant to the development of therapeutics for Friedreich’s ataxia.
These results reveal an unexpected mechanism that replaces FXN-based stimulation of the Fe-S cluster biosynthetic pathway and suggest new strategies to overcome the loss of cellular FXN that may be relevant to the development of therapeutics for Friedreich’s ataxia.
Tuesday, April 2, 2019
L’ataxie de Friedreich : la particularité subsaharienne
Ale Thiam, Amadou Koura Ndao, Mansour Ndiaye, Fatou Diouf Sene, Amadou Gallo Diop, Ibrahima Pierre Ndiaye, Astou Thiam, Revue Neurologique, Volume 175, Supplement 1, 2019, Page S127, doi:10.1016/j.neurol.2019.01.333.
Notre prévalence de cas d’AF est faible. La symptomatologie était moindre au Sénégal comparativement à la population caucasienne. Cependant, la conscientisation de la population autour des facteurs socio-ethniques est nécessaire.
Notre prévalence de cas d’AF est faible. La symptomatologie était moindre au Sénégal comparativement à la population caucasienne. Cependant, la conscientisation de la population autour des facteurs socio-ethniques est nécessaire.
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