Deadlines for the FARA Grant Program
are Approaching 
LOIs for the Keith Michael Andrus (KMA) Cardiac Award, the Kyle Bryant (KB) Translational Research Award, and the Bronya J. Keats (BJK) Research Collaboration Award are due on January 15. 

KMA Cardiac Award: Proposals focused on advancing understanding and/or treatment of the cardiac involvement in FA 

KB Translational Research Award: Proposals focused on pre-clinical and clinical investigations that will advance treatments for FA, such as the identification of biomarkers, the development of tools and technologies that can be used for therapy development, the pre-clinical development and testing of potential therapeutics, or clinical studies of patient outcome measures. 

BJK Research Collaboration Award: Proposals focused on FA research that relies on the collaboration among investigators from at least two different Institutions. Special consideration will be given to proposals that bring new scientists to the FA community. 

The Award for Innovative Mindset (AIM) application deadline is February 1.
  
The AIM supports the initial exploration of innovative, high-risk, high-gain, and potentially groundbreaking concepts in FA research. The presentation of preliminary and/or published data is encouraged, but not required. Note that this application does not require an LOI.  

LOIs for General Grants, Postdoctoral Fellowships, and Postdoctoral Awards are due on February 15.
 
All investigators interested in FA-related research are invited to submit an LOI through our submission portal.
Pharma News
Exicure, Inc. Announces Results of Internal Investigation and Implementation of Strategic Measures to Reduce Cash Burn and Prioritize Pipeline Focus 

The Audit Committee of the Board of Directors of Exicure announced the findings of the internal investigation initiated and overseen by the Audit Committee and conducted by outside counsel in connection with alleged improprieties that Grant Corbett, Ph.D., the Company’s former Group Lead of Neuroscience, claimed to have committed with respect to the Company’s XCUR-FXN preclinical program for the treatment of Friedreich’s ataxia. Beginning in the autumn of 2020, Dr. Corbett misreported raw data from certain research and development experiments related to XCUR-FXN. Dr. Corbett misreported the results of at least three different experiments that were conducted through at least February 2021. Company management reasonably relied on Dr. Corbett’s analysis when making public statements that included Dr. Corbett’s misreported data. 

Read the full press release here. 
FARA Funded Research
Epigenetic Heterogeneity in Friedreich Ataxia Underlies Variable FXN Reactivation.  
Rodden LN, Gilliam KM, Lam C, Lynch DR, Bidichandani SI. 

This study shows that treatment of PBMCs from a prospective cohort of 50 FRDA patients with a class I histone deacetylase inhibitor (HDACi-109) significantly increased FXN transcript to levels seen in asymptomatic heterozygous carriers, albeit with inter-individual variability. Response to HDACi-109 correlated significantly with the prevalence of unmethylated and partially methylated FXN molecules, supporting the model that FXN reactivation involves a proportion of genes that are amenable to correction in non-dividing somatic cells, and that heavily methylated FXN molecules are relatively resistant to reactivation.  
The Responsiveness of Gait and Balance Outcomes to Disease Progression in Friedreich Ataxia.  
Milne SC, Kim SH, Murphy A, Larkindale J, Farmer J, Malapira R, Danoudis M, Shaw J, Ramakrishnan T, Rasouli F, Yiu EM, Georgiou-Karistianis N, Tai G, Zesiewicz T, Delatycki MB, Corben LA. 

This study aims at identifying gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA). The authors administered a battery of potential measures three times over a 12-month period. Outcomes included GAITRite® spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25-Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS).  
Other FA Research Publications, December 2021
Rad9-mediated checkpoint activation is responsible for elevated expansions of GAA repeats in CST-deficient yeast.  
Spivakovsky-Gonzalez E, Polleys EJ, Masnovo C, Cebrian J, Molina-Vargas AM, Freudenreich CH, Mirkin SM. 

This study characterized the effect of the temperature-sensitive cdc13-1 mutation on GAA repeat instability in yeast. This mutation leads to ∼10-fold increase in the rate of large-scale expansions of repeats. The authors hypothesize that increased repeat expansions in the cdc13-1 mutant happen during post-replicative repair of nicks or small gaps within repetitive tracts during the G2 phase of the cell cycle upon activation of the G2/M checkpoint. 
Pharmacotherapy of cerebellar and vestibular disorders.  
Lemos J, Manto M. 

This article provides a review on therapeutic advances in patients with episodic and progressive cerebellar ataxias from the last two years.  
A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's ataxia.  
Campos OA, Attar N, Cheng C, Vogelauer M, Mallipeddi NV, Schmollinger S, Matulionis N, Christofk HR, Merchant SS, Kurdistani SK. 

Here, the authors report that histone H3–mediated Cu1+ toxicity is a major determinant of cellular functional pool of Fe-S clusters. These findings reveal an interplay between chromatin and mitochondria in Fe-S cluster homeostasis and a potential pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S cluster dysfunction. 
The Dynamin-Related Protein 1 is Decreased and the Mitochondrial Network is Altered in Friedreich's Ataxia Cardiomyopathy.  
Chidipi B, Angulo MB, Shah SI, Rieser M, Ullah G, McDonald TV, Noujaim SF 

This study found a significantly higher mitochondrial footprint, decreased mitochondrial fission dynamin-related protein, and mitochondrial fission rate over fusion with more giant mitochondrial clusters in human induced pluripotent stem cell derived cardiomyocytes from a patient with Friedreich ataxia hypertrophic cardiomyopathy, compared to an unaffected individual.  
Characterizing cardiac phenotype in Friedreich's ataxia: The CARFA study.  
Legrand L, Weinsaft JW, Pousset F, Ewenczyk C, Charles P, Hatem S, Heinzmann A, Biet M, Durr A, Redheuil A. 

The aim of this study is to characterize the cardiac phenotype associated with Friedreich's ataxia, and to assess the evolution of the associated cardiopathy over 1 year. The multivariable characterization of the cardiac phenotype of patients with Friedreich's ataxia was significantly different from controls at baseline. Over 1 year there were no clinically significant changes in patients with Friedreich's ataxia compared with healthy controls, whereas the neurological severity score increased modestly. 
Friedreich's Ataxia Frequency in a Large Cohort of Genetically Undetermined Ataxia Patients. 
Brown AF, Parkinson MH, Garcia-Moreno H, Mudanohwo E, Labrum R, Sweeney M, Giunti P. 

This study aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia center either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process. This study demonstrates that FRDA is very rare among patients who were referred purely for SCA testing without the clinical suspicion of FRDA.  
Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders. 
Seminotti B, Grings M, Tucci P, Leipnitz G, Saso L. 

This review focuses on the current knowledge about Nrf2 signaling dysregulation observed in Inherited Metabolic Disorders characterized by neurological dysfunction. This paper reviews Nrf2 signaling alterations observed in X-linked adrenoleukodystrophy, glutaric acidemia type I, hyperhomocysteinemia, and Friedreich's ataxia.   
A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase.  
Doni D, Meggiolaro M, Santos J, Audran G, Marque SRA, Costantini P, Bortolus M, Carbonera D. 

In this work, the authors use site-directed spin labelling coupled to electron paramagnetic resonance spectroscopy (SDSL-EPR) and fluorescence quenching experiments to investigate the interaction between human FXN and superoxide dismutase (SOD2) in vitro. This study provides evidence that human FXN interacts with human SOD2 in vitro and that the complex is in fast exchange.  
Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich's Ataxia.  
Bogdanova-Mihaylova P, Plapp HM, Chen H, Early A, Cassidy L, Walsh RA, Murphy SM. 

This study evaluated a cohort of patients with FRDA to characterize the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). The results highlight that FDRA is associated with subclinical optic neuropathy and progressive retinal nerve fiber layer (RNFL) thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA. 
The FARA Forum Webinars
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: 
 
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 

March 8, 2022 
12:00 PM ET Sanjay Bidichandani, University of Oklahoma
FARA Newly Awarded Research Grants  
General research grants 
Mirella Dottori, PhD – University of Wollongong, Australia 
Investigating Proprioceptor Development and Function in Friedreich’s Ataxia 

Postdoctoral Research Award
Dezhen Wang, PhD – University of Pennsylvania 
Unveil the link between lipid metabolism and cardiomyopathy in Friedreich’s ataxia using patient-specific iPSC-CMs.
Meetings of Interest to the FA Community
The Ataxia Global Initiative (AGI) is holding a webinar series called Young Investigator initiative (YII). The next webinar “NGS analysis in ataxias: what it is and how it is done” will be held on Tuesday, January 18, 2022 at 9pm CET.  
You can register and find more information on upcoming webinars here.

2022 MDA Clinical & Scientific Conference, March 13 - 16, 2022  
 
American Society of Gene & Cell Therapy, May 16-19, 2022 - WASHINGTON, D.C. 

Neurodegeneration: The Biological Pathways Driving the Future of Therapeutic Development, joint with Neuro-Immune Interactions in the Central Nervous System, Keystone CO June 05 - 09, 2022 
Grant Opportunities
  • 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.

Wellcome Trust funding opportunities. Application deadlines:
  • Early-Career Awards - February 15, 2022

Job Advertisements
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 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.
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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