Request For Proposals:
Pharmacodynamic Biomarker Development
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FARA is issuing a request for proposal (RFP) to support the discovery and validation of non-invasive and quantitative methodologies to measure the following in FRDA affected tissues (brain, spinal cord or heart):
- Frataxin protein levels
- Biochemical activities dependent on/downstream of frataxin function that can be surrogates of frataxin in inaccessible tissues.
You can access the full RFP here.
Please submit a Letter of Intent here.
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ICAR Abstract Submission Opens
September 9, 2021
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The National Ataxia Foundation (NAF), the Friedreich’s Ataxia Research Alliance (FARA), and Ataxia UK are pleased to host the inaugural International Congress for Ataxia Research (ICAR) to be held at the Caribe Royale resort in Orlando, Florida, USA. Please save the date for March 15th – 18th, 2022.
Key dates:
September 9, 2021: Abstract Submission opens
September 16, 2021: Registration opens
November 8, 2021: Abstract Submission Deadline (11:59 pm ET)
December 15, 2021: Abstract Acceptance Announced
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United Against Ataxia Hill Day |
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We invite you to join NAF and FARA in raising awareness about Ataxia and supporting legislation that directly impacts our communities.
The third United Against Ataxia Hill Day will be held on Wednesday, September 29, 2021. It will be a virtual event so every US resident, regardless of where you are, can participate. There is no cost or need to travel. Instead, you can speak to your Congressional Members right from the comforts of your home!
What Happens at Hill Day?
A group of advocates will meet with Congressional Members to discuss issues important to the Ataxia community. This year's topics will include:
1.A Senate Resolution to declare September 25th as National Ataxia Awareness Day (S.Res. 339)
2.The addition of "Hereditary Ataxia" into the Congressionally Directed Medical Research Program (CDMRP)
Your voice is needed to pass these important initiatives! No experience needed! NAF and FARA will be running a Hill Day Advocacy training webinar prior to the event. Access information will be sent to registrants at a later date.
Registration for this event will close on September 20, 2021. Don't miss the chance to join us, register today!
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Reata Pharmaceuticals, Inc. Announces Second Quarter 2021 Financial Results and Provides an Update on Clinical Development Programs |
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Based on a communication received from the U.S. Food and Drug Administration (“FDA”) regarding omaveloxolone for the treatment of FA, Reata withdrew the request for a Type C meeting and requested a pre-NDA meeting with the FDA. The pre-NDA meeting request has been granted, a pre-NDA meeting has been scheduled during the third quarter of this year, and Reata has submitted briefing materials for the meeting. Reata recently received a communication from the FDA requesting the estimated date of the New Drug Application (“NDA”) for its planning purposes. Reata plans to submit the NDA during the first quarter of 2022.
See the press release here.
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Design Therapeutics Reports GeneTAC™ Portfolio Progress and Second Quarter 2021 Results |
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Design Therapeutics reported recent progress with its portfolio of novel small molecule gene targeted chimeras (GeneTACsTM), as well as business highlights and second quarter 2021 financial results.
New data from IND-enabling studies with GeneTACTM product candidate for Friedreich Ataxia (FA) support initiation of clinical trial in first half of 2022. Data from IND-enabling studies in rodents and non-human primates showed that multidose systemic administration of the company’s FA GeneTAC was well tolerated and achieved higher concentrations in the CNS (cerebrum, cerebellum, brainstem and spinal cord), heart, and skeletal muscle than needed to restore frataxin (FXN) gene expression.
See the press release here.
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Other FA Research Publications, August 2021 |
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Digital endpoints for self-administered home-based functional assessment in pediatric Friedreich's ataxia.
Mueller A, Paterson E, McIntosh A, Praestgaard J, Bylo M, Hoefling H, Wells M, Lynch DR, Rummey C, Krishnan ML, Schultz M, Malanga CJ.
This study evaluated the utility of home-based, self-administered digital endpoints in children with Friedreich's ataxia and unaffected controls and their relationship to standard clinical rating scales. Domains analyzed were hand motor function with a digitized drawing, automated analysis of speech with a recorded oral diadochokinesis test, and gait and balance with wearable sensors.
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Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions.
Tarnacka B, Jopowicz A, Maślińska M.
In this review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. This paper describes diseases related to these metals, including Friedreich's ataxia.
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The Role of Voltage-Dependent Anion Channel in Mitochondrial Dysfunction and Human Disease.
Varughese JT, Buchanan SK, Pitt AS.
This review covers the current understanding of the various states of the voltage-dependent anion channel (VDAC), VDAC interaction partners, and the roles they play in mitochondrial regulation pertaining to human diseases. The interaction partners of VDAC, together with the permeability of the pore, affect the molecular pathology of diseases including Parkinson's disease (PD), Friedreich's ataxia (FA), lupus, and cancer.
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Diagnostic and Prognostic Value of Cardiovascular Magnetic Resonance in Neuromuscular Cardiomyopathies.
Almogheer B, Antonopoulos AS, Azzu A, Al Mohdar S, Vlachopoulos C, Pantazis A, Mohiaddin RH.
In this study, the authors explored the diagnostic and prognostic value of Cardiovascular Magnetic Resonance (CMR) in neuromuscular disease (NMD)-related cardiomyopathies. This study presents data from a unique cohort of NMD patients and provides evidence on the incidence, patterns, and the prognostic value of late gadolinium enhancement (LGE) in NMD-related cardiomyopathy. LGE is variably present in NMD subtypes and correlates with LV remodeling, dysfunction, and clinical outcomes in patients with NMD.
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Polyuria and Acute Hyperglycemia Secondary to New-Onset Diabetes in a Young Woman With Friedreich's Ataxia.
Santos J, Woloski JR, Wu N.
This is a case study of a 23-year-old woman with progressive Friedreich's ataxia (FRDA) who presented to a local urgent care facility for urinary urgency and frequency. A urinalysis showed the presence of trace ketones and glucose, and point-of-care testing revealed severely elevated glucose. She was diagnosed with new-onset diabetes mellitus and started on insulin therapy.
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SS-31 efficacy in a mouse model of Friedreich ataxia by upregulation of frataxin expression.
Liu Y, Cai J, Shen J, Dong W, Xu L, Fang M, Lin Y, Liu J, Ding Y, Qiao T, Li K.
In this study, the authors used the GAA expansion-based models including Y47 and YG8R mice, primary neurons and macrophages from the mice and cells derived from FRDA patients to explore the therapeutic potential of SS-31, a mitochondrion-targeted peptide. After once-daily intraperitoneal injection of 1 mg/kg SS-31 for one month, the study showed significant improvement of motor function. The vacuolation in dorsal root ganglia, lesions in dentate nuclei and the lost thickness of myelin sheath of spinal cord were all repaired after SS-31 treatment. Interestingly, the authors found that SS-31 treatment upregulated FXN expression.
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Treatment with ROS detoxifying gold quantum clusters alleviates the functional decline in a mouse model of Friedreich ataxia.
Villa C, Legato M, Umbach A, Riganti C, Jones R, Martini B, Boido M, Medana C, Facchinetti I, Barni D, Pinto M, Arguello T, Belicchi M, Fagiolari G, Liaci C, Moggio M, Ruffo R, Moraes CT, Monguzzi A, Merlo GR, Torrente Y.
This paper shows that systemic delivery of catalysts activity of gold cluster superstructures (Au8-pXs) improves cell response to mitochondrial reactive oxygen species and thereby alleviates FRDA-related pathology in mesenchymal stem cells from patients with FRDA. The study also found that systemic injection of Au8-pXs ameliorated motor function and cardiac contractility of YG8sR mouse model that recapitulates the FRDA phenotype. These effects were associated to long-term improvement of mitochondrial functions and antioxidant cell responses. These events were related to an increased expression of frataxin, which was sustained by reduced autophagy.
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Mechanisms of impaired mitochondrial homeostasis and NAD+ metabolism in a model of mitochondrial heart disease exhibiting redox active iron accumulation.
Chiang S, Braidy N, Maleki S, Lal S, Richardson DR, Huang ML.
This investigation examined the muscle creatine kinase conditional frataxin knockout mouse to dissect the mechanisms of dysfunctional mitochondrial homeostasis. Dysfunction of key mitochondrial homeostatic mechanisms were elucidated in the knockout hearts relative to wild-type littermates, namely: (1) mitochondrial proliferation with condensed cristae; (2) impaired NAD+ metabolism due to perturbations in Sirt1 activity and NAD+ salvage; (3) increased mitochondrial biogenesis, fusion and fission; and (4) mitochondrial accumulation of Pink1/Parkin with increased autophagic/mitophagic flux.
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Neuro-Ophthalmological Findings in Friedreich's Ataxia.
Rojas P, de Hoz R, Cadena M, Salobrar-García E, Fernández-Albarral JA, López-Cuenca I, Elvira-Hurtado L, Urcelay-Segura JL, Salazar JJ, Ramírez JM, Ramírez AI.
This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.
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Brain Structure and Degeneration Staging in Friedreich Ataxia: MRI Volumetrics from the ENIGMA-Ataxia Working Group.
Harding IH, Chopra S, Arrigoni F, Boesch S, Brunetti A, Cocozza S, Corben LA, Deistung A, Delatycki M, Diciotti S, Dogan I, Evangelisti S, França MC Jr, Göricke SL, Georgiou-Karistianis N, Gramegna LL, Henry PG, Hernandez-Castillo CR, Hutter D, Jahanshad N, Joers JM, Lenglet C, Lodi R, Manners DN, Martinez AR, Martinuzzi A, Marzi C, Mascalchi M, Nachbauer W, Pane C, Peruzzo D, Pisharady PK, Pontillo G, Reetz K, Rezende TJ, Romanzetti S, Saccà F, Scherfler C, Schulz JB, Stefani A, Testa C, Thomopoulos SI, Timmann D, Tirelli S, Tonon C, Vavla M, Egan GF, Thompson PM.
This group of investigators undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA, using magnetic resonance imaging. Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles; subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation.
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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:
September 14, 2021
12:00 PM EDT Ronald Crystal, Weill Cornell Medical College
12:45 PM EDT Shannon Boye, University of Florida
October 12, 2021
12:00 PM ET Robert Wilson, Children's Hospital of Philadelphia
12:45 PM ET Chad Heatwole, University of Rochester Medical Center
November 9, 2021
12:00 PM ET Joseph Baur, University of Pennsylvania
12:45 PM ET Shana McCormack, Children's Hospital of Philadelphia
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FARA Newly Awarded Research Grants |
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Postdoctoral fellowship
Chen Liang, PhD – University of Rochester
Pathophysiology of Muscle Dysfunction in Friedreich’s Ataxia
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Meetings of Interest to the FA Community |
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Neuroscience 2021, November 13-16, 2021 - McCormick Place Convention Center, Chicago.
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
Stem Cell Network (Canada) - 2022-2025 Research Funding Competition will open on September 1st, 2021
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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