Thank you for celebrating FA awareness day by attending the FARA Flash Talks in May. This year’s presentation prizes will go to:
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Tyler Perfitt – Pfizer - A new mouse model to study heart failure in FA
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Elizabeth Mercado - University of Pennsylvania - Studying the brain of an FA mouse model
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Kristian Want - CNRS-CEA-Université Paris-Saclay - Searching for frataxin-replacing molecules through virtual screening
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Shweta Sahni - AIIMS, New Delhi and CSIR-IGIB, New Delhi - Blood-based inflammation as a biomarker for FA clinical trials
Congratulations and thank you to all of the junior investigators who participated!
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New Deadlines for the FARA Grant Program |
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FARA is announcing new deadlines for the Keith Michael Andrus Cardiac Award (KMA), the Kyle Bryant Translational Research Award (KB) and the Bronya J. Keats Research Collaboration Award (BJK).
Proposals for the KMA award should focus on advancing understanding and/or treatment of the cardiac disease in FA.
The KB award is given to proposals focused on pre-clinical and clinical investigations that will advance treatments for FA. These include: identification of biomarkers and outcome measures, development of tools and technologies that can be used or applied to therapy development, pre-clinical development and testing of potential therapeutics.
The BJK award aims to promote collaboration. Proposals must be a joint effort of investigators from at least two different institutions. Special consideration will be given to proposals that involve international collaborations and bring new scientists to the FA community.
LOIs are due by November 1, 2023.
General Research Grants, Postdoctoral Fellowships and Research Awards LOI are due by August 15, 2023.
Click here for more information.
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PTC Therapeutics Announces Topline Results from Vatiquinone MOVE-FA Registration-Directed Trial
PTC Therapeutics reported topline results from the MOVE-FA trial of vatiquinone in patients with Friedreich ataxia. The study did not meet its primary endpoint of statistically significant change in mFARS score at 72 weeks in the primary analysis population. However, vatiquinone treatment did demonstrate significant benefit on key disease subscales and secondary endpoints. Overall, vatiquinone was demonstrated to be well tolerated, adding to the large volume of safety data collected in other pediatric clinical studies.
Click here for the full press release.
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Recent FARA Funded FA Publications
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Frataxin deficiency disrupts mitochondrial respiration and pulmonary endothelial cell function.
Culley MK, Rao RJ, Mehta M, Zhao J, El Khoury W, Harvey LD, Perk D, Tai YY, Tang Y, Shiva S, Rabinovitch M, Gu M, Bertero T, Chan SY.
Here, the authors aim to identify the mitochondria-specific effects of FXN deficiency in the endothelium that predispose to pulmonary hypertension. These data highlight an Fe-S-driven metabolic shift separate from previously described replication stress whereby FXN knockdown diminished mitochondrial respiration and increased glycolysis and oxidative species production. This study indicates that FXN is an upstream driver of pathologic aberrations in metabolism and genomic stability.
Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.
Munoz-Zuluaga C, Gertz M, Yost-Bido M, Greco A, Gorman N, Chen A, Kooner V, Rosenberg JB, De BP, Kaminsky SM, Bborczuk A, Ricart Arbona R, Martin HR, Monette S, Khanna R, Barth JA, Crystal RG, Sondhi D.
This study aimed at identifying both minimally and significantly effective therapeutic doses of AAVrh.10hFXN that are clinically relevant for the treatment of the cardiac manifestations of FA in the MCK mouse. The minimally effective dose was 5.7x1011 gc/kg, resulting in cardiac human FXN levels of 6.1±4.2 ng/mg and a mild (p<0.01 compared to PBS controls) improvement in mortality. A dose of 1.8x1012 gc/kg resulted in cardiac human FXN levels of 33.7±6.4 ng/mg, a significant improvement in ejection fraction and fractional shortening (p<0.05, both comparisons), and a 21.5% improvement in mortality (p<0.001).
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Omaveloxolone: First Approval.
Lee A.
This article summarizes the milestones in the development of omaveloxolone leading to this first approval for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.
Omaveloxolone (SkyclarysTM) for patients with Friedreich's ataxia.
Dayalan Naidu S, Dinkova-Kostova AT.
This article is a brief overview of Omaveloxolone and its mechanism of action.
Neuropsychiatric symptoms in spinocerebellar ataxias and Friedreich ataxia.
Simona K, Veronika M, Zahinoor I, Martin V.
This narrative review summarizes the current knowledge on neuropsychiatric impairment in SCA and FRDA. The authors discuss the prevalence, clinical features and treatment approaches in the most commonly reported domains of depression, anxiety, apathy, agitation and impulse dyscontrol, and psychosis.
Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study.
Ortega Suero G, Abenza Abildúa MJ, Serrano Munuera C, Rouco Axpe I, Arpa Gutiérrez FJ, et al.
This study aimed to determine the prevalence of ataxia and hereditary spastic paraplegia in Spain in 2019.
Short-read genome sequencing allows 'en route' diagnosis of patients with atypical Friedreich ataxia.
Fleszar Z, Dufke C, Sturm M, Schüle R, Schöls L, Haack TB, Synofzik M.
This study shows how the introduction of short-read genome sequencing (SR-GS) allows to overcome biases in the work-up of complex ataxias, as it allows to detect even intronic short-tandem repeat-expansions (STRs) (i) “en route”, i.e. with detection not requiring any primary direct gene analysis; and (ii) in a phenotype-independent fashion”, i.e. also for those atypical phenotypic presentations where the corresponding gene and mutational mechanism had not been part of the prior differential clinical diagnosis.
Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich's Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress.
Lew SY, Mohd Hisam NS, Phang MWL, Syed Abdul Rahman SN, Poh RYY, Lim SH, Kamaruzzaman MA, Chau SC, Tsui KC, Lim LW, Wong KH.
This study aimed to investigate the protective effects of adenosine against mitochondrial dysfunction and impaired mitochondrial biogenesis in L-buthionine sulfoximine (BSO)-induced oxidative stress in dermal fibroblasts derived from an FRDA patient. Adenosine improves mitochondrial function and biogenesis, leading to cellular iron homeostasis.
A Milestone in the Treatment of Ataxias: Approval of Omaveloxolone for Friedreich Ataxia.
Subramony SH, Lynch DL.
This article examines the US FDA approval of omaveloxolone for FA and the generated discussion about outcome measures, biomarkers, trial design, and the nature of approval process for inherited ataxias.
Large-scale expansions of Friedreich's ataxia GAA•TTC repeats in an experimental human system: role of DNA replication and prevention by LNA-DNA oligonucleotides and PNA oligomers.
Rastokina A, Cebrián J, Mozafari N, Mandel NH, Smith CIE, Lopes M, Zain R, Mirkin SM.
Here the authors describe an experimental system to analyze large-scale repeat expansions in cultured human cells. Locked nucleic acid (LNA)-DNA mixmer oligonucleotides and peptide nucleic acid (PNA) oligomers, which interfere with triplex formation at GAA•TTC repeats in vitro, prevented the expansion of these repeats in human cells.
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FARA Newly Awarded Research Grants |
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Postdoctoral Fellowship
Amy Hulme, University of Wollongong
Investigating the Mechanosensory System in Friedreich’s Ataxia using Stem Cell Models
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Meetings of Interest to the FA Community |
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General Research Grants, Postdoctoral Fellowships and Research Awards – LOI deadline is August 15, 2023.
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KMA Cardiac Award, KB Translational Research Award and BJK Research Collaboration Award – LOI deadline is November 1, 2023.
See FARA grant program priorities here.
The Raynor Cerebellum Project is a new initiative that invites applications from collaborative teams in order to bring together research teams and clinicians with the goal of treating individuals with cerebellar disorders. LOIs are due by June 23, 2023.
The French Association for Friedreich's Ataxia (AFAF) and the Foundation for Rare Diseases (FMR) are partnering to support research on Friedreich's ataxia. The deadline for submission is June 22, 2023.
FDA launched the FDA Rare Neurodegenerative Disease Grant Program. The agency awards grants and contracts to public and private entities to cover costs of research and development of interventions intended to prevent, diagnose, mitigate, treat or cure ALS and other rare neurodegenerative diseases in adults and children.
Grant opportunities from CIRM can be found here.
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Postdoctoral positions at UT Southwestern – Napierala lab
Two postdoctoral fellow positions are immediately available to work on oligonucleotide-mediated therapeutic approaches for Friedreich’s ataxia (FRDA), one of the most common inherited ataxias, caused by expansion of trinucleotide repeats. The postdoctoral fellow will also be involved in developing approaches for gene replacement therapy for FRDA. Both projects involve work with state-of-the-art induced pluripotent stem cell (iPSC)-based models and/or mouse models of the disease. We are seeking highly motivated scientists to join our multi-disciplinary group at the University of Texas Southwestern Medical Center in Dallas, TX to advance development of cure for FRDA.
The position requires experience utilizing mammalian cell culture models, general molecular and cellular biology techniques and/or experience working with transgenic mouse models. Expertise in culture of iPSCs or in applications involving antisense oligonucleotides, genome editing, viral expression vectors, transcriptional regulation and post-translational histone modifications is desirable but not required.
We offer competitive pay starting at $55,000 per year plus insurance and a comprehensive benefits package. Successful candidates will be eligible for an additional award of $10,000 per year for up to three years. In addition, postdoctoral fellows will be able to participate in two conferences per year (expenses paid).
The Department of Neurology at UT Southwestern Medical Center is a nationally recognized leader in the comprehensive management of neurological conditions. Our vibrant Department comprises more than 75 full-time faculty in 12 subspecialty sections, supporting a spectrum of complex and innovative approaches to neurological care, a broad range of novel research programs, and abundant educational opportunities for trainees. Through collaborations with the Peter O’Donnell Jr. Brain Institute, the Department of Neurology is building state-of-the art facilities for drug and device testing and bringing current and new faculty together for collaborative research on brain disease therapy.
Dallas is an extremely vibrant, cosmopolitan metropolis of more than 10 million people and is home to world class restaurants, art and professional sports.
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