We're excited to add a new section to the newsletter- Meet the Community. Each month, we'll introduce you to someone living with FA to help share the patient and family perspectives. This month, in the below video, let's meet the fun and insightful Juip Family from Michigan. |
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Call for Abstracts for the
2022 FARA Flash Talk Series
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During the month of May, to celebrate FA Awareness Month, FARA will host the third annual Flash Talks series. These webinars will feature presentations from graduate students, postdocs, and residents involved in FA research. This is a great chance for FA patients, caregivers, and friends to learn about FARA funded research and get to know and interact with junior investigators involved in FA research. The primary audience for these flash talks is the FA patient and caregiver community, so presentations should be understandable for a lay audience.
We encourage all postdocs, grad students and residents working in the FA field to express their interest in participating by submitting a short abstract via the link below, by March 1, 2022. Speakers will be notified by March 21, 2022.
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Reata Pharmaceuticals Initiates Rolling Submission of New Drug Application with U.S. FDA for Omaveloxolone for the Treatment of Patients with Friedreich’s Ataxia
Reata Pharmaceuticals announced that the company has initiated a rolling submission of a New Drug Application (“NDA”) to the U.S. FDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia. The rolling submission allows Reata to submit portions of the regulatory application to the FDA for review on an ongoing basis. The company reiterates that it expects to complete the submission of the NDA by the end of the first quarter of 2022.
Read the full press release here.
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The attitude of patients with progressive ataxias towards clinical trials.
Thomas-Black G, Dumitrascu A, Garcia-Moreno H, Vallortigara J, Greenfield J, Hunt B, Walther S, Wells M, Lynch DR, Montgomery H, Giunti P.
In this article the authors sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. This study conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich's Ataxia Research Alliance (FARA) sent the survey to their members. Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
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Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders.
Shah S, Dooms MM, Amaral-Garcia S, Igoillo-Esteve M.
In this article, the authors discuss the scientific, regulatory, and economic aspects of the development of repurposed drugs for the treatment of rare neurodegenerative disorders with a particular focus on Huntington's disease, Friedreich's ataxia, Wolfram syndrome, and amyotrophic lateral sclerosis. The role of academia, pharmaceutical companies, patient associations, and foundations in the identification of candidate compounds and their preclinical and clinical evaluation is also discussed.
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Transcriptional Analysis of Nuclear-Encoded Mitochondrial Genes in Eight Neurodegenerative Disorders: The Analysis of Seven Diseases in Reference to Friedreich's Ataxia.
Elsadany M, Elghaish RA, Khalil AS, Ahmed AS, Mansour RH, Badr E, Elserafy M.
In this study, the authors analyzed the transcriptional changes of nuclear-encoded mitochondrial (NEM) genes in eight neurodegenerative diseases (NDDs) to specifically address the association of these genes with the diseases. Differential gene expression analysis and pathway enrichment analysis was carried out to pinpoint differentially expressed genes that are potentially associated with one or more of the analyzed NDDs. These findings propose a strong link between NEM genes and NDDs and suggest that the identified candidate genes can be potentially used as diagnostic markers and therapeutic targets.
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Mice harboring the FXN I151F pathological point mutation present decreased frataxin levels, a Friedreich ataxia-like phenotype, and mitochondrial alterations.
Medina-Carbonero M, Sanz-Alcázar A, Britti E, Delaspre F, Cabiscol E, Ros J, Tamarit J.
In this study, the authors introduced the I151F mutation into the murine Fxn gene (equivalent to human I154F) and analyzed the consequences of this pathological point mutation in vivo. FXNI151F homozygous mice present low frataxin levels in all tissues, with no evidence of insoluble proteoforms. Moreover, they display neurological deficits resembling those observed in FA patients.
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During FeS-cluster biogenesis ferredoxin and frataxin use overlapping bindings sites on yeast cysteine desulfurase Nfs1.
Uzarska MA, Grochowina I, Soldek J, Jelen M, Schilke B, Marszalek J, Craig EA, Dutkiewicz R.
Here, based on the results of biochemical experiments involving purified wild-type and variant proteins, the authors report that in Saccharomyces cerevisiae ferredoxin (Yah1) and frataxin (Yfh1) share an evolutionary conserved interaction site on Nfs1. Consistent with this notion, Yah1 and Yfh1 can each displace the other from Nfs1, but are inefficient competitors when a variant with an altered interaction site is used.
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Hsa-miR223-3p circulating level is upregulated in Friedreich's ataxia and inversely associated with HCLS1 associated protein X-1, HAX-1.
Quatrana A, Morini E, Tiano F, Vancheri C, Panarello L, Romano S, Marcotulli C, Casali C, Mariotti C, Mongelli A, Fichera M, Rufini A, Condò I, Novelli G, Testi R, Amati F, Malisan F.
This study carried out a miRNA PCR-array analysis of plasma samples of early-, intermediate- and late-onset FRDA groups, defining a set of 30 differentially expressed miRNAs. Hsa-miR223-3p is the only miRNA shared between the three patient groups and appears upregulated in all of them. A significant positive correlation between hsa-miR223-3p expression and cardiac parameters in typical FRDA patients (onset < 25 years) was found. Moreover, a significant negative correlation between hsa-miR223-3p expression and HAX-1 (HCLS1 associated protein X-1) at mRNA and protein level was observed in all FRDA patients. In silico analyses suggested HAX-1 as a target gene of hsa-miR223-3p.
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Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?
Rodríguez LR, Lapeña-Luzón T, Benetó N, Beltran-Beltran V, Pallardó FV, Gonzalez-Cabo P, Navarro JA.
In this article, the authors highlight the importance of Ca2+ signaling in mitochondria and how the mechanism of communication in endoplasmic reticulum-mitochondria-associated membranes (MAMs) is pivotal for mitochondrial maintenance and cell homeostasis. They also describe potential targets located in MAMs and different therapeutic strategies focused on restoring mitochondrial Ca2+ uptake as an emergent approach for neurological diseases.
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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:
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
March 8, 2022
12:00 PM ET Sanjay Bidichandani, University of Oklahoma
April 12, 2022
12:00 PM ET Masimo Pandolfo, McGill University
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FARA Newly Awarded Research Grants
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General Research Grants
Shawn Liu, PhD – Columbia University & Joriene de Nooij – Columbia University
Rescue of Friedreich’s Ataxia cells by DNA methylation editing of the FXN gene
Xinnan Wang, PhD – Stanford University
Novel Mitochondrial Targets for Friedreich’s Ataxia
David Lynch, MD, PhD – Children’s Hospital of Philadelphia
Understanding ketogenesis in FRDA: Pathophysiology, biomarkers and nutritional therapies
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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 “Standard clinical assessment in ataxia” will be held on Tuesday February 22, 2022 at 5pm CET. You can register and find more information on upcoming webinars here.
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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.
Wellcome Trust funding opportunities. Application deadlines: Early-Career awards - Feb 15, 2022, Wellcome Discovery - Mar 24, 2022, Wellcome Career Development Awards - Mar 29, 2022
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Research Scientist postion open 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 a job opening for a Research Scientist. 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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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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