New deadlines for the FARA grant program
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LOIs for the Keith Michael Andrus Cardiac Award, the Kyle Bryant Translational Research Award, and the Bronya J. Keats International Research Collaboration Award: January 15
Award for Innovative Mindset applications: February 1
LOIs for General Grants, Postdoctoral Fellowships, and Postdoctoral Awards: February 15 and August 15.
Please see more information, including grant funding start dates for each cycle here.
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It is with exceptional disappointment that we have announced the postponement of ICAR 2022 until later in the year. The ICAR host organizations are committed to providing a high-quality scientific conference. We believe that having a fully in-person meeting is required to meet our educational and community building objectives.
The continuously evolving guidelines and restrictions around international travel, particularly with the recent emergence of the Omicron variant, make planning participation for our attendees very challenging. We want to have a conference when all who want to attend are able to do so with greater confidence.
Thank you for your support and patience as we work to bring you a safe and rewarding in-person experience. We will keep you updated about plans to reschedule.
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Reata Pharmaceuticals Receives Fast Track Designation From the FDA for Omaveloxolone for the Treatment of Friedreich’s Ataxia
Reata Pharmaceuticals, Inc. a clinical-stage biopharmaceutical company, announced that the U.S. Food and Drug Administration has granted Fast Track Designation for omaveloxolone for the treatment of Friedreich’s ataxia. The Fast Track program is designed to accelerate the development and review of products such as omaveloxolone, which are intended to treat serious diseases and for which there is an unmet medical need. Fast Track Designation enables more frequent communication with the FDA and eligibility for FDA programs such as priority review and rolling review, if relevant criteria are met.
Reata remains committed to submitting the New Drug Application during the first quarter of 2022 and continues working with the FDA to secure regulatory approval as quickly as possible. You can read the full press release here.
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Conformational stability, dynamics and function of human frataxin: Tryptophan side chain interplay.
Espeche LD, Sewell KE, Castro IH, Capece L, Pignataro MF, Dain L, Santos J.
This work analyzes three frataxin variants in which one tryptophan was replaced by a glycine: W155G, W168G and W173G. As expected, given its localization in the assembly site, W155G was not able to activate the desulfurase activity of the supercomplex for iron-sulfur cluster assembly. In turn, W168G, which was significantly more unstable than W155G, was fully active. W173G, which was as highly unstable as W168G, showed a significantly decreased activity, only slightly higher than W155G. They observed that W173G may display altered motions at the Trp155 site. The authors suggest that this motion modulation can be directly transferred to the assembly site, altering the dynamics of the ISCU His137 key residue. The authors propose that the supercomplex requires very definite motions of Trp155 to consolidate the assembly site.
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Cellular pathophysiology of Friedreich's ataxia cardiomyopathy.
Lees JG, Napierala M, Pébay A, Dottori M, Lim SY.
Here, the authors review available evidence regarding the current understanding of cellular mechanisms and the involvement of cardiac non-myocytes in the pathogenesis of FRDA cardiomyopathy. At the cellular level, cardiomyocyte hypertrophy, apoptosis and fibrosis contribute to the cardiac pathology. However several clinical studies have reported the involvement of cardiac non-myocytes such as vascular cells, autonomic neurons, and inflammatory cells in the pathogenesis of FRDA cardiomyopathy.
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Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study.
Patel M, McCormick A, Tamaroff J, Dunn J, Mitchell JA, Lin KY, Farmer J, Rummey C, Perlman SL, Delatycki MB, Wilmot GR, Mathews KD, Yoon G, Hoyle J, Corti M, Subramony SH, Zesiewicz T, Lynch D, McCormack SE.
This study tested the association between body mass index (BMI) and height and clinical characteristics in FRDA. A substantial proportion of children (17%) were underweight, and female sex was associated with lower BMI-Z. In adults, older age was associated with higher BMI. In children, older age and worse modified Friedreich Ataxia Rating Scale (mFARS) scores were associated with shorter stature. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset and longer GAA repeat length were associated with shorter stature.
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Other FA Research Publications, November 2021 |
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Left atrial appendage thrombosis in a patient with Friedreich Ataxia-related cardiomyopathy, left ventricular systolic dysfunction, and atrial fibrillation.
Russo M, Nuzzo A, Foschi M, Boarin S, Lorenzetti S, Tomasi C, Querzani P, Rubboli A.
The authors present the case of a 45-year-old man with a history of paroxysmal atrial fibrillation and a congestive heart failure, hypertension, CHA2DS2-VASc score of only 1 who presented with pneumonia and was also found to have atrial fibrillation with a rapid ventricular response. This case suggests that the risk of thromboembolism in Friedreich ataxia subjects with atrial fibrillation may not be adequately predicted by the sole CHA2DS2-VASc score.
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History of Ataxias and Paraplegias with an Annotation on the First Description of Striatonigral Degeneration.
Berciano J, Gazulla J, Infante J.
The aim of this paper is to carry out a historical overview of the evolution of the knowledge on degenerative cerebellar disorders and hereditary spastic paraplegias, over the last century and a half.
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Objective Assessment of Progression and Disease Characterization of Friedreich Ataxia via an Instrumented Drinking Cup: Preliminary Results.
Krishna R, Pathirana PN, Horne MK, Szmulewicz DJ, Corben LA.
In this feasibility study, an Ataxia Instrumented Measurement-Cup (AIM-C) is proposed to quantify the disease progression of 10 participants with FRDA (mean age 39 years, onset of disease 16.3 years) in longitudinal timepoints. The device consists of a sensing system with the provision of extracting both kinetic and kinematic information while engaging in an activity closely associated with activities of daily living (ADL). Both kinetic and kinematic measures captured clinically relevant features and correlated 85% with clinical assessments.
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Diagnosis and Management of Cardiovascular Involvement in Friedreich Ataxia.
Monda E, Lioncino M, Rubino M, Passantino S, Verrillo F, Caiazza M, Cirillo A, Fusco A, Di Fraia F, Fimiani F, Amodio F, Borrelli N, Mauriello A, Natale F, Scarano G, Girolami F, Favilli S, Limongelli G.
This review aims to describe the current state of knowledge regarding cardiovascular involvement of FRDA, focusing on clinical-instrumental features and management of cardiac manifestation.
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Molecular approaches for the treatment and prevention of Friedreich's ataxia.
Yang W, Thompson B, Kwa FAA.
Here, the authors discuss various molecular approaches that target the molecular pathways that silence FXN and downstream pathological processes, and explore their therapeutic potential to alter the course of FRDA.
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Mitochondrial iron metabolism and neurodegenerative diseases.
Cheng R, Dhorajia V, Kim J, Kim Y.
This review provides an update on the causal effects of iron overload in the development and progression of neurodegenerative diseases and discusses important roles of mitochondrial iron homeostasis in Huntington's disease, Alzheimer's disease, Parkinson's disease, and Friedreich's ataxia. Furthermore, this review discusses potential therapeutic targets for the treatments of iron overload-linked neurodegenerative diseases.
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Clinical and Molecular Features of First Mexican Friedreich's Ataxia Patients with Compound Heterozygous FXN Mutations.
Boll MC, Gasca-Saldaña D, Mayén-Lobo YG, Dávila-Ortiz de Montellano DJ, Monroy-Jaramillo N.
This study aims to present data on FXN variants observed in patients with sporadic or recessive ataxia, including detailed data of the first compound heterozygous (CH) Mexican patients.
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Body Mass Index and Height in Friedreich Ataxia: What Do We Know?
Boesch SM, Indelicato E.
This is a commentary on the paper “Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study” published in Neurology Genetics.
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Source of medical information and behavioral seeking patterns in patients affected with Friedreich's ataxia and their caregivers: a survey study.
Miele G, Lavorgna L, De Mercanti SF, Iudicello M, Abbadessa G, Matta M, Bonavita S, Clerico M.
The aim of this study was to improve the quality of the information for FRDA patients and caregivers and suggest a possible tool to spread this information.
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Myocardial and Arrhythmic Spectrum of Neuromuscular Disorders in Children.
Baban A, Lodato V, Parlapiano G, di Mambro C, Adorisio R, Bertini ES, Dionisi-Vici C, Drago F, Martinelli D.
In this review, the authors selected and described five specific Neuromuscular disorders: Friedreich's Ataxia, congenital and childhood forms of Myotonic Dystrophy type 1, Kearns Sayre Syndrome, Ryanodine receptor type 1-related myopathies and Laminopathies. For each described disorder, the focus was on the possible cardiac manifestations such as different types of cardiomyopathies, structural heart abnormalities, and progressive heart rhythm changes. The current management strategies for these conditions are described.
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Molecular characteristics of proteins within the mitochondrial Fe-S cluster assembly complex.
Hinton TV, Batelu S, Gleason N, Stemmler TL.
Here the authors summarize what is known about the structure and functional activities of the proteins involved in the early steps of assembling [2Fe-2S] clusters before they are transferred to proteins devoted to their delivery. The goal is to provide a comprehensive overview of how the ISC assembly apparatus proteins interact to make the Fe-S cluster which can be delivered to proteins downstream to the assembly event.
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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. Here are the next dates:
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
January 11, 2022
5:00 PM ET Elena Dedkova, University of California, Davis
5:45 PM ET Jarmon Lees, St Vincent's Institute of Medical Research, Melbourne
February 8, 2022
12:00 PM ET Stephen Chan, University of Pittsburgh School of Medicine
12:45 PM ET Thiago Rezende, University of Campinas, Brazil
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Meetings of Interest to the FA Community |
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The Ataxia Global Initiative (AGI) is holding a webinar series called Young Investigator initiative (YII). The next webinar “Magnetic resonance imaging in clinical care and research of ataxias” will be held on December 14 at 9 pm CET.
You can register and find more information on upcoming webinars here.
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FARA research grants: KMA Cardiac Award, KB Translational Research Award and BJK International Research Collaboration Award – LOI deadline is January 15, 2022; Award for Innovative Mindset – application deadline is February 1, 2022; General Research Grants – next LOI deadline is February 15, 2022. See FARA grant program priorities here.
CIRM - Various grant opportunities for stem cell-related projects in California.
- Early-Career Awards - February 15, 2022
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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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Several open positions in the Napierala laboratory - UT Southwestern Medical Center, Department of Neurology
The Napierala laboratory, now located at UT Southwestern’s Peter O’Donnell Jr Brain Institute, has various job openings. The research is focused on Friedreich’s ataxia, specifically on the use of cell culture models, including induced pluripotent stem cells, and mouse models to study molecular mechanisms underlying the pathology of the disease. The primary aspects of the research include transcriptional regulation, mitochondria dysfunction and protein structure/function analyses and the use of multiple -omics approaches to identify new targets for therapeutic intervention.
The laboratory is also looking for postdocs and any interested candidate is welcome to send an email directly to Dr. Marek Napierala (mnapiera@uab.edu) or Dr. Jill Napierala (jsbutler@uab.edu) to inquire.
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