ICAR 2022: Abstract submission and registration are now open
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The inaugural International Congress for Ataxia Research (ICAR) will be held at the Caribe Royale resort in Orlando, Florida, USA. Please save the date for March 15th – 18th, 2022.
Travel bursaries and poster awards are available for junior investigators, i.e. students, postdocs of 5 or fewer years (accounting for career disruptions), medical residents or fellows and working in a mentored environment. To apply for a travel bursary when submitting an abstract upload one pdf file that includes your CV and a very brief statement expressing your interest and indicating any financial constraints that would prevent your attendance. You can submit your abstract and register here. Abstract submission deadline is November 8, 2021.
COVID-19 Information
COVID-19 is a rapidly evolving situation. The ICAR Planning Committee is still planning and preparing for an in-person congress with a live stream of main stage presentations. However, we are developing contingency plans that will allow a quick response to changing conditions. These include postponing the event or pivoting to a fully virtual conference. We plan to provide further updates by the end of 2021 and recommend that attendees do not book non-refundable travel until that time.
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Reata Pharmaceuticals Plans NDA Submission for Omaveloxolone in First Quarter of 2022 Following Completion of Pre-NDA Meeting with FDA
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Reata Pharmaceuticals, a clinical-stage biopharmaceutical company, announced that it has completed its pre-New Drug Application (“NDA”) meeting with the United States Food and Drug Administration (“FDA”) for omaveloxolone for the treatment of patients with Friedreich’s ataxia and reaffirmed its plan to submit an NDA in the first quarter of 2022.
The purpose of the pre-NDA meeting was to discuss the content of Reata’s planned NDA submission. Reata plans to submit the NDA seeking standard approval for omaveloxolone for the treatment of Friedrich’s ataxia, and is not planning to conduct a second pre-approval clinical study prior to the submission. The FDA indicated that the appropriate approval pathway would be a matter of review after submission of the NDA. You can read the full press release here.
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LEXEO Therapeutics Closes $100 Million Series B Financing |
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Proceeds from the financing will support the development of LEXEO’s expanded pipeline, including recently acquired cardiac gene therapy programs and additional preclinical programs focused on the genetic causes of Alzheimer’s disease (LX1020 and LX1021). The financing will also advance the company’s three lead investigational AAV-mediated gene therapy programs through clinical development to meaningful value inflection points: LX2006, an IV-administered gene therapy for cardiomyopathy associated with Friedreich’s ataxia (FA), LX1004, a central nervous system (CNS)-administered gene therapy for CLN2 Batten disease and LX1001, a CNS- administered gene therapy for APOE4-associated Alzheimer’s disease.
See the press release here.
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Age of onset modulates resting-state brain network dynamics in Friedreich Ataxia.
Naeije G, Coquelet N, Wens V, Goldman S, Pandolfo M, De Tiège X.
This magnetoencephalography study addresses (i) how Friedreich ataxia (FRDA) affects the sub-second dynamics of resting-state brain networks, (ii) the main determinants of their dynamic alterations, and (iii) how these alterations are linked with FRDA-related changes in resting-state functional brain connectivity over long timescales. In FRDA patients, a positive correlation was found between the age of symptoms onset (ASO) and the temporal dynamics of two hidden Markov modeling states involving the posterior default mode network and the temporo-parietal junctions. This study demonstrates that ASO is the main determinant of alterations in the sub-second dynamics of posterior associative neocortices in FRDA patients and substantiates a direct link between sub-second network activity and functional brain integration over long timescales.
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Adaptation of the heart to Frataxin depletion: Evidence that integrated stress response can predominate over mTORC1 activation.
Vásquez-Trincado C, Patel M, Sivaramakrishnan A, Bekeová C, Anderson-Pullinger L, Wang N, Tang HY, Seifert EL.
In this study the authors modified a transgenic (TG) mouse model of inducible FXN depletion that permits phenotypic evaluation of the heart at different FXN levels, and focused on substrate-specific bioenergetics and stress signaling. When FXN protein in the TG heart was ~ 97% depleted, TG heart mass and cardiomyocyte cross-sectional area were less, without evidence of fibrosis or apoptosis. mTORC1 signaling was activated, as was the integrated stress response. These results suggest that, in TG hearts, an anabolic stimulus was constrained by eIF2α phosphorylation. Altogether, these findings suggest that the FXN depleted heart can suppress a major ATP demanding process such as protein translation, which, together with some preservation of β-oxidation, could be adaptive, at least in the short term.
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Other FA Research Publications, September 2021 |
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Three Adult-Onset Autosomal Recessive Ataxias: What Adult Neurologists Need to Know
Paulus-Andres JA, Burnett MS.
This review seeks to raise awareness of 3 autosomal recessive ataxias, late-onset Tay-Sachs disease, very late-onset Friedreich ataxia, and autosomal recessive spastic ataxia of Charlevoix-Saguenay that look different clinically when presenting in adulthood rather than childhood. This review covers their genetics, clinical presentation, and necessary diagnostic steps.
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A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation.
Li L, Conradson DM, Bharat V, Kim MJ, Hsieh CH, Minhas PS, Papakyrikos AM, Durairaj AS, Ludlam A, Andreasson KI, Partridge L, Cianfrocco MA, Wang X.
This paper reports an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress.
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Plasma idebenone monitoring in Friedreich's ataxia patients during a long-term follow-up.
Paredes-Fuentes AJ, Cesar S, Montero R, Latre C, Genovès J, Martorell L, Cuadras D, Colom H, Pineda M, Del Mar O'Callaghan M, Sarquella-Brugada G, Darling A, Artuch R.
This study reports plasma idebenone values in a cohort of Friedreich's ataxia (FRDA) patients during a long-term follow-up. Cardiological and neurological status were also assessed. The authors did not find a consistent positive effect after analysis of paired data at the beginning and the end of the study.
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Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis.
Peng L, Wang S, Chen Z, Peng Y, Wang C, Long Z, Peng H, Shi Y, Hou X, Lei L, Wan L, Liu M, Zou G, Shen L, Xia K, Qiu R, Tang B, Ashizawa T, Klockgether T, Jiang H.
This study is a meta-analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia, including spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and ataxia telangiectasia (A-T).
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The FARA Forum is a monthly webinar featuring investigators who have been awarded FARA grants. The webinar is open to FARA grant awardees, and it is held on the second Tuesday of every month. Upcoming Dates:
November 9, 2021
12:00 PM ET Joseph Baur, University of Pennsylvania
12:45 PM ET Shana McCormack, Children's Hospital of Philadelphia
December 14, 2021
12:00 PM ET Vania Broccoli, San Raffaele Scientific Institute and CNR Institute of Neuroscience, Milan
12:45 PM ET Katia Aquilano, University of Rome Tor Vergata
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Meetings of Interest to the FA Community |
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Save the date for the inaugural International Congress for Ataxia Research (ICAR), March 15-18, 2022 - Orlando, Florida, USA.
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RFP –Pharmacodynamic biomarker development – LOI deadline is December 1, 2021;
- Keith Michael Andrus Cardiac Award – next LOI deadline is January 15, 2022;
- General Research Grants – next LOI deadline is February 1, 2022.
See FARA grant program priorities here
CIRM - Various grant opportunities for stem cell-related projects in California.
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Post-doctoral fellow position – Mouro Pinto Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School
The Mouro Pinto Laboratory in the Center for Genomic Medicine at Massachusetts General Hospital and Harvard Medical School is seeking a highly motivated post-doctoral fellow candidate. The Lab is interested in repeat expansion disorders, such as Friedreich Ataxia and Huntington’s disease, with a major focus on the mechanisms responsible for repeat instability as potential therapeutic targets. The Lab uses both mouse and patient-derived cellular models, in combination with genome engineering tools, viral-based delivery techniques, and next-generation sequencing methods to identify genetic disease modifiers and develop novel methods for unbiased quantification of long somatic repeat expansions.
The major goal of this project is to determine the role of somatic FXN GAA repeat expansions in Friedreich ataxia-related phenotypes and testing of candidate therapeutics targeting this pathway. The ideal candidate would have significant expertise in various molecular biology techniques, animal handling, and mammalian cell culturing. Desirable skills also include gene expression analysis (RT-qPCR and RNAseq), differentiation of iPS cells, immunohistochemistry, CRISPR/Cas9-based genome editing, and bioinformatics analysis.
We offer competitive pay at NIH recommended level and assistance with visa application for international candidates. Interested applicants should contact Dr. Mouro Pinto (rmouropinto@mgh.harvard.edu) directly with their CV, a summary of their research accomplishments, and a brief description of research interests and career goals.
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Post-doctoral fellow position - Napierala Laboratory, University of Alabama at Birmingham
A post-doctoral fellow position is immediately available to study mechanisms of Friedreich’s ataxia in the Napierala Laboratory, within the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham. We are seeking a highly motivated scientist to join our multi-disciplinary group who is interested in investigating how chromatin changes are implicated in the pathogenesis of repeat expansion diseases.
The position requires experience utilizing mammalian cell culture models, and proficiency working with induced pluripotent stem cells is desirable. Preference will be given to candidates demonstrating expertise in chromatin biology, transcriptional regulation and post-translational histone modifications, including experience performing ChIP, ChIP-seq and RNAseq experiments.
The postdoctoral fellow duties will include but are not limited to: organizing and implementing complex research plans (independently and as part of a team), developing new methods, collecting and recording data, and analyzing and critically interpreting data. The successful candidate will be expected to possess excellent communication skills and present their research findings regularly to peers within the Department and at national and international meetings. The postdoctoral fellow will also participate in preparation of grant applications and publications.
We offer competitive pay at or above NIH recommended level and relocation assistance.
To be considered for this position, please email your CV and cover letter to mnapiera@uab.edu.
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